KR102283767B1 - Pharmaceutical composition for preventing, treating and inhibiting metastasis of breast cancer comprising fermented soybean extract suppressing PLAU and ERBB2 expressions - Google Patents
Pharmaceutical composition for preventing, treating and inhibiting metastasis of breast cancer comprising fermented soybean extract suppressing PLAU and ERBB2 expressions Download PDFInfo
- Publication number
- KR102283767B1 KR102283767B1 KR1020190065726A KR20190065726A KR102283767B1 KR 102283767 B1 KR102283767 B1 KR 102283767B1 KR 1020190065726 A KR1020190065726 A KR 1020190065726A KR 20190065726 A KR20190065726 A KR 20190065726A KR 102283767 B1 KR102283767 B1 KR 102283767B1
- Authority
- KR
- South Korea
- Prior art keywords
- breast cancer
- protein
- plau
- erbb2
- extract
- Prior art date
Links
- 206010006187 Breast cancer Diseases 0.000 title claims abstract description 74
- 208000026310 Breast neoplasm Diseases 0.000 title claims abstract description 74
- 206010027476 Metastases Diseases 0.000 title claims abstract description 64
- 230000009401 metastasis Effects 0.000 title claims abstract description 62
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 37
- 230000014509 gene expression Effects 0.000 title claims description 45
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 24
- 235000020712 soy bean extract Nutrition 0.000 title description 15
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 title description 6
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 title description 6
- 238000000034 method Methods 0.000 claims abstract description 22
- 102100031358 Urokinase-type plasminogen activator Human genes 0.000 claims description 72
- 108090000623 proteins and genes Proteins 0.000 claims description 67
- 102000004169 proteins and genes Human genes 0.000 claims description 64
- 101000638886 Homo sapiens Urokinase-type plasminogen activator Proteins 0.000 claims description 62
- 239000000284 extract Substances 0.000 claims description 47
- 235000010469 Glycine max Nutrition 0.000 claims description 43
- 244000068988 Glycine max Species 0.000 claims description 42
- 230000000694 effects Effects 0.000 claims description 30
- 102000001301 EGF receptor Human genes 0.000 claims description 23
- 108060006698 EGF receptor Proteins 0.000 claims description 23
- 241000194108 Bacillus licheniformis Species 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 13
- 230000004850 protein–protein interaction Effects 0.000 claims description 10
- 230000005764 inhibitory process Effects 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 8
- 238000010208 microarray analysis Methods 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 4
- 238000003012 network analysis Methods 0.000 claims description 3
- 238000012216 screening Methods 0.000 claims 3
- 101800003838 Epidermal growth factor Proteins 0.000 claims 1
- 102100033237 Pro-epidermal growth factor Human genes 0.000 claims 1
- 229940116977 epidermal growth factor Drugs 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 28
- 235000013305 food Nutrition 0.000 abstract description 9
- 210000004027 cell Anatomy 0.000 description 42
- 235000018102 proteins Nutrition 0.000 description 42
- 201000011510 cancer Diseases 0.000 description 34
- 206010028980 Neoplasm Diseases 0.000 description 31
- 239000004480 active ingredient Substances 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 201000010099 disease Diseases 0.000 description 6
- 238000002493 microarray Methods 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 210000000481 breast Anatomy 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 4
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 210000002744 extracellular matrix Anatomy 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 108090000397 Caspase 3 Proteins 0.000 description 3
- 102000003952 Caspase 3 Human genes 0.000 description 3
- CLSDNFWKGFJIBZ-YUMQZZPRSA-N Gln-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(N)=O CLSDNFWKGFJIBZ-YUMQZZPRSA-N 0.000 description 3
- 108010065920 Insulin Lispro Proteins 0.000 description 3
- AIXUQKMMBQJZCU-IUCAKERBSA-N Lys-Pro Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O AIXUQKMMBQJZCU-IUCAKERBSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108010073771 Soybean Proteins Proteins 0.000 description 3
- 244000299461 Theobroma cacao Species 0.000 description 3
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- -1 for example Substances 0.000 description 3
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 229960005356 urokinase Drugs 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 2
- 102000001938 Plasminogen Activators Human genes 0.000 description 2
- 108010001014 Plasminogen Activators Proteins 0.000 description 2
- 101000834248 Takifugu rubripes Actin, cytoplasmic 1 Proteins 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000004709 cell invasion Effects 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 235000019219 chocolate Nutrition 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 210000005075 mammary gland Anatomy 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229940127126 plasminogen activator Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 235000019710 soybean protein Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 108091012583 BCL2 Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 1
- 102100037904 CD9 antigen Human genes 0.000 description 1
- 102100028914 Catenin beta-1 Human genes 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102100024361 Disintegrin and metalloproteinase domain-containing protein 9 Human genes 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 101150086923 ERB1 gene Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 1
- 101000738354 Homo sapiens CD9 antigen Proteins 0.000 description 1
- 101000916173 Homo sapiens Catenin beta-1 Proteins 0.000 description 1
- 101000832769 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 9 Proteins 0.000 description 1
- 101000998629 Homo sapiens Importin subunit beta-1 Proteins 0.000 description 1
- 101001013150 Homo sapiens Interstitial collagenase Proteins 0.000 description 1
- 102100033258 Importin subunit beta-1 Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 206010073099 Lobular breast carcinoma in situ Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 102100038124 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 208000028715 ductal breast carcinoma in situ Diseases 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 238000013332 literature search Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 201000010879 mucinous adenocarcinoma Diseases 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 229940001941 soy protein Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/07—Tetrapeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/54—Proteins
- A23V2250/548—Vegetable protein
- A23V2250/5488—Soybean protein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
Abstract
본 발명은 PLAU 단백질 및 ERBB2 단백질의 발현 또는 활성을 억제하는 대두 발효 추출물을 유효성분으로 포함하는 유방암의 예방, 치료 또는 전이억제용 약학적 조성물, 유방암의 예방, 개선 또는 전이억제용 식품 조성물, 및 유방암의 치료 또는 전이 억제 방법에 관한 것이다.The present invention relates to a pharmaceutical composition for preventing, treating or inhibiting metastasis of breast cancer, a food composition for preventing, improving or inhibiting metastasis, and It relates to a method of treating or inhibiting metastasis of breast cancer.
Description
본 발명은 PLAU 단백질 및 ERBB2 단백질의 발현을 억제하는 대두 발효 추출물을 유효성분으로 포함하는 유방암의 예방, 치료 또는 전이억제용 약학적 조성물에 관한 것으로, 더욱 상세하게는 PLAU 단백질 또는 ERBB2 단백질의 발현 또는 활성을 억제하는 대두 발효 추출물을 유효성분으로 포함하는 유방암의 예방, 치료 또는 전이억제용 약학적 조성물, 유방암의 예방, 개선 또는 전이억제용 식품 조성물, 및 유방암의 치료 또는 전이 억제 방법에 관한 것이다.The present invention relates to a pharmaceutical composition for preventing, treating or inhibiting metastasis of breast cancer comprising, as an active ingredient, a fermented soybean extract that inhibits expression of PLAU protein and ERBB2 protein, and more particularly, expression of PLAU protein or ERBB2 protein or The present invention relates to a pharmaceutical composition for preventing, treating or inhibiting metastasis of breast cancer, a food composition for preventing, improving, or inhibiting metastasis of breast cancer, and a method for treating or inhibiting metastasis of breast cancer, which comprises a fermented soybean extract that inhibits activity as an active ingredient.
유방암(breast cancer)은 유방에 발생하는 모든 악성 종양을 통틀어 말하는 것으로, 유방에 비정상적인 세포조직이 계속 자라거나 다른 장기로 퍼지는 치명적인 질병이다. 한국 여성들에게 있어서 유방암 발병률은 갑상선 암에 이어서 두 번째이며, 유방암 발병률은 20대 및 30대에서 증가하다가 40대에서 최고에 이른다. Breast cancer refers to all malignant tumors that occur in the breast, and is a fatal disease in which abnormal cell tissues continue to grow in the breast or spread to other organs. For Korean women, the incidence of breast cancer is second only to thyroid cancer, and the incidence of breast cancer increases in their 20s and 30s, and then peaks in their 40s.
유방암의 치료는 조기 진단시 외과적 절제술로 치료가 가능하나 많은 환자에서 폐, 뼈, 간 등 원격적인 전이 형태로 재발된다. 암 세포의 전이(metastasis)는 암 치료를 어렵게 하는데, 이 때 세포를 둘러싸고 있는 조직으로 침투해 들어가는 세포 침윤(invasion) 과정이 필수적이며 이는 악성 암세포의 특징 중 하나이다(Aznavoorian et al., Cancer 71,1368-1383, 1993). 암세포의 침윤성에는 세포외 기질(extracellular matrix, ECM)과 기저막(basement membrane)을 분해하는 단백질 분해과정과 분해된 매트릭스(matrix)를 통하여 이동하는 세포 이동성(migration)이 관여한다.When diagnosed early, breast cancer can be treated with surgical resection, but in many patients, it recurs in the form of distant metastases such as lung, bone, and liver. Metastasis of cancer cells makes it difficult to treat cancer. At this time, the process of cell invasion that penetrates into the tissue surrounding the cells is essential, which is one of the characteristics of malignant cancer cells (Aznavoorian et al., Cancer 71, 1368-1383, 1993). The invasiveness of cancer cells involves proteolysis that decomposes the extracellular matrix (ECM) and the basement membrane, and cell migration through the decomposed matrix.
이러한 유방암의 예방 및 치료용 약학적 조성물에 대한 종래 기술로서, 등록특허 제0909998호는 아라자임을 유효성분으로 하는 유방암 예방 및 치료용 약학적 조성물에 대하여 개시하고 있다. 그러나, 이러한 종래 기술은 상기 조성물이 사전에 어떤 단백질의 발현에 영향을 미치는지 예측하기 어렵다는 점에서 유방암 치료제 개발에 어려움이 있었다.As a prior art for a pharmaceutical composition for preventing and treating breast cancer, Patent Registration No. 0909998 discloses a pharmaceutical composition for preventing and treating breast cancer using arazyme as an active ingredient. However, this prior art has had difficulties in developing a therapeutic agent for breast cancer in that it is difficult to predict in advance which protein the composition will affect the expression of.
이에 본 발명자들은 유방암세포의 마이크로어레이 데이터(microarray data)와 잘 알려진 유방암 전이 마커를 합쳐서 새로운 연결망을 제조하고 이러한 연결망 분석을 통해 유방암세포를 청국장 추출물로 처리하고 PLAU와 ERBB2 단백질의 발현정도를 측정한 결과 청국장 추출물이 PLAU와 ERBB2 단백질의 발현을 억제한다는 것을 확인함으로써 본 발명을 완성하였다.Therefore, the present inventors prepared a new network by combining the microarray data of breast cancer cells and well-known breast cancer metastasis markers. Results The present invention was completed by confirming that the cheonggukjang extract inhibits the expression of PLAU and ERBB2 protein.
따라서 본 발명의 목적은 PLAU(plasminogen activator, urokinase) 단백질 또는 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제하는 대두 발효 추출물을 유효성분으로 포함하는 유방암의 예방, 치료 또는 전이억제용 약학적 조성물, 유방암의 예방, 개선 또는 전이억제용 식품 조성물 및 유방암의 치료 또는 전이 억제 방법을 제공하는데 있다.Accordingly, an object of the present invention is to provide a pharmaceutical for preventing, treating or inhibiting metastasis of breast cancer comprising, as an active ingredient, a fermented soybean extract that inhibits the expression or activity of PLAU (plasminogen activator, urokinase) protein or ERBB2 (epidermal growth factor receptor 2) protein. An object of the present invention is to provide a food composition for preventing, improving or inhibiting metastasis of breast cancer, and a method for treating or inhibiting metastasis of breast cancer.
본 발명의 다른 목적은 PLAU(plasminogen activator, urokinase) 단백질의 발현 또는 활성 억제제를 유효성분으로 포함하는 유방암의 예방, 치료 또는 전이억제용 약학적 조성물을 제공하는데 있다.Another object of the present invention is to provide a pharmaceutical composition for preventing, treating or inhibiting metastasis of breast cancer comprising an inhibitor of PLAU (plasminogen activator, urokinase) protein expression or activity as an active ingredient.
상술한 목적을 달성하기 위한 본 발명의 바람직한 일 실시예에 따른 유방암의 예방, 치료 또는 전이억제용 약학적 조성물은 PLAU(plasminogen activator, urokinase) 단백질 및 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제하는 대두 발효 추출물을 유효성분으로 포함한다.The pharmaceutical composition for preventing, treating, or inhibiting metastasis of breast cancer according to a preferred embodiment of the present invention for achieving the above object is PLAU (plasminogen activator, urokinase) protein and ERBB2 (epidermal growth factor receptor 2) protein expression or It contains a soybean fermented extract that inhibits activity as an active ingredient.
본 발명의 바람직한 다른 실시예에 따른 유방암의 예방, 치료 또는 전이억제용 약학적 조성물은 PLAU(plasminogen activator, urokinase) 단백질의 발현 또는 활성 억제제를 유효성분으로 포함한다.The pharmaceutical composition for preventing, treating, or inhibiting metastasis of breast cancer according to another preferred embodiment of the present invention includes an inhibitor of PLAU (plasminogen activator, urokinase) protein expression or activity as an active ingredient.
또한, 본 발명에 따른 유방암의 예방, 치료 또는 전이억제용 약학적 조성물에 있어서, 상기 대두 발효 추출물은 Bacillus licheniformis 균주로 대두를 발효시킨 추출물인 것을 특징으로 한다.In addition, in the pharmaceutical composition for preventing, treating, or inhibiting metastasis of breast cancer according to the present invention, the fermented soybean extract is an extract obtained by fermenting soybeans with a Bacillus licheniformis strain.
또한, 본 발명에 따른 유방암의 예방, 치료 또는 전이억제용 약학적 조성물에 있어서, 상기 대두 발효 추출물은 Bacillus licheniformis 균주로 대두를 발효시킨 대두 발효물을 에탄올로 추출하여 제조된 청국장 추출물이고, 상기 대두 발효 추출물은 Ala-Phe-Pro-Gly, Gly-Val-Ala-Trp-Trp-Met-Tyr, Lys-Pro 및 Gln-Lys 으로 이루어진 군 중에서 1종 이상 선택되는 펩타이드를 포함하는 것을 특징으로 한다.In addition, in the pharmaceutical composition for preventing, treating, or inhibiting metastasis of breast cancer according to the present invention, the fermented soybean extract is a cheonggukjang extract prepared by extracting with ethanol a soybean fermented product obtained by fermenting soybeans with a strain of Bacillus licheniformis, and the soybean The ferment extract is characterized in that it contains one or more peptides selected from the group consisting of Ala-Phe-Pro-Gly, Gly-Val-Ala-Trp-Trp-Met-Tyr, Lys-Pro and Gln-Lys.
또한, 본 발명에 따른 유방암의 예방, 치료 또는 전이억제용 약학적 조성물에 있어서, 상기 조성물이 유방암 세포의 성장 억제 및 전이(metastasis) 억제 효과를 갖는 것을 특징으로 한다.In addition, in the pharmaceutical composition for preventing, treating or inhibiting metastasis of breast cancer according to the present invention, the composition is characterized in that it has an effect of inhibiting growth of breast cancer cells and inhibiting metastasis.
본 발명의 바람직한 다른 실시예에 따른 유방암의 예방, 개선 또는 전이억제용 식품 조성물은 PLAU(plasminogen activator, urokinase) 단백질 및 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제하는 대두 발효 추출물을 유효성분으로 포함한다.A food composition for preventing, improving, or inhibiting metastasis of breast cancer according to another preferred embodiment of the present invention comprises a fermented soybean extract that inhibits the expression or activity of PLAU (plasminogen activator, urokinase) protein and ERBB2 (epidermal growth factor receptor 2) protein. included as an active ingredient.
또한, 본 발명에 따른 유방암의 예방, 개선 또는 전이억제용 식품 조성물에 있어서, 상기 대두 발효 추출물은 Bacillus licheniformis B1 균주로 대두를 발효시킨 추출물인 것을 특징으로 한다.In addition, in the food composition for preventing, improving, or inhibiting metastasis of breast cancer according to the present invention, the fermented soybean extract is an extract obtained by fermenting soybeans with a Bacillus licheniformis B1 strain.
본 발명의 바람직한 다른 실시예에 따른 유방암의 치료 또는 전이 억제 방법은 PLAU(plasminogen activator, urokinase) 단백질 및 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제하는 대두 발효 추출물을 인간을 제외한 개체에 투여하는 단계를 포함한다.The method of treating or inhibiting metastasis of breast cancer according to another preferred embodiment of the present invention comprises administering a soybean ferment extract that inhibits the expression or activity of PLAU (plasminogen activator, urokinase) protein and ERBB2 (epidermal growth factor receptor 2) protein to an individual other than a human. including the step of administering to
또한, 본 발명에 따른 유방암의 치료 또는 전이 억제 방법에 있어서, 상기 대두 발효 추출물은 Bacillus licheniformis B1 균주로 대두를 발효시킨 대두 발효물을 에탄올로 추출하여 제조된 청국장 추출물인 것을 특징으로 한다.In addition, in the method for treating or inhibiting metastasis of breast cancer according to the present invention, the fermented soy extract is a soybean fermented product obtained by fermenting soybeans with a Bacillus licheniformis B1 strain, and is characterized in that it is a cheonggukjang extract prepared by extracting with ethanol.
본 발명에 따르면, 본 발명의 대두 발효 추출물을 유효성분으로 포함하는 유방암의 예방, 치료 또는 전이억제용 약학적 조성물, 유방암의 예방, 개선 또는 전이억제용 식품 조성물 및 유방암의 치료 또는 전이 억제 방법은 PLAU(plasminogen activator, urokinase) 단백질 또는 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제할 수 있다.According to the present invention, a pharmaceutical composition for preventing, treating or inhibiting metastasis of breast cancer, a food composition for preventing, improving or inhibiting metastasis of breast cancer, and a method for treating or inhibiting metastasis of breast cancer, comprising the fermented soybean extract of the present invention as an active ingredient It can inhibit the expression or activity of PLAU (plasminogen activator, urokinase) protein or ERBB2 (epidermal growth factor receptor 2) protein.
또한, 본 발명의 유방암의 예방, 치료 또는 전이억제용 약학적 조성물은 PLAU(plasminogen activator, urokinase) 단백질의 발현 또는 활성을 억제할 수 있다.In addition, the pharmaceutical composition for preventing, treating, or inhibiting metastasis of breast cancer of the present invention can inhibit the expression or activity of PLAU (plasminogen activator, urokinase) protein.
도 1은 본 발명의 일 실시예에 따른 연결망(네트워크) 분석도이다. 암전이 마커와 관련된 단백질은 붉은색으로 표시되고, 발효된 대두의 마이크로어레이 데이터 기반 연결망에서 유래한 단백질은 청색으로 표시되었다. 녹색 단백질은 암전이 마커 단백질과 마이크로어레이 단백질을를 연결한다. 노란색은 암전이 및 마이크로 어레이데이터 기반 연결망(네트워크) 단백질임을 표시한다.
도 2는 본 발명의 일 실시예에 따른 PLAU 및 ERBB2의 발현을 나타내는 그래프이다. (A)는 PLAU 발현 결과이다. MCF7 세포에서 PLAU mRNA의 증폭을 위한 실시간 PCR이 수행되었다. β- 액틴 mRNA는 내부 컨트롤로서 증폭되었다. 0.1 mg/ml 대두 발효 추출물(P) 및 무첨가(C)로 처리된 MCF7 세포에서 PLAU 발현을 실시간 PCR 수행 후 비교되었다. C의 값은 1이고 P의 값은 0.46이다. (B)는 ERBB2 발현 결과이다. MCF7 세포에서 ERBB2 mRNA의 증폭을 위한 실시간 PCR이 수행되었다. 0.1 mg/ml 대두 발효 추출물(P) 및 무첨가(C)로 처리된 MCF7 세포에서 ERBB2 발현을 실시간 PCR 수행 후 비교되었다. C의 값은 1이고 P의 값은 0.30이다.
도 3은 본 발명의 일 실시예에 따른 NO 분석 결과이다. MCF7 세포를 0.5 mg/ml 대두 발효 추출물로 1일(0.5) 처리하였다. 세포를 NO 형광 분석 프로브에 넣고 1.5 시간 동안 저장하였다. FITC 필터가 장착된 형광 현미경(DMi8, Leica)을 이용하여 세포 이미지 (A), (B)를 얻었다. Image J 프로그램을 사용하여 세포의 강도를 측정하였다(C).1 is a diagram illustrating a connection network (network) analysis according to an embodiment of the present invention. Proteins related to cancer metastasis markers are shown in red, and proteins derived from microarray data-based networks of fermented soybeans are shown in blue. The green protein connects the cancer metastasis marker protein and the microarray protein. Yellow indicates cancer metastasis and microarray data-based network (network) protein.
2 is a graph showing the expression of PLAU and ERBB2 according to an embodiment of the present invention. (A) is the result of PLAU expression. Real-time PCR for the amplification of PLAU mRNA in MCF7 cells was performed. β-actin mRNA was amplified as an internal control. PLAU expression in MCF7 cells treated with 0.1 mg/ml soybean ferment extract (P) and additive-free (C) was compared after performing real-time PCR. The value of C is 1 and the value of P is 0.46. (B) is the result of ERBB2 expression. Real-time PCR for amplification of ERBB2 mRNA in MCF7 cells was performed. ERBB2 expression in MCF7 cells treated with 0.1 mg/ml soybean ferment extract (P) and no addition (C) was compared after performing real-time PCR. The value of C is 1 and the value of P is 0.30.
3 is a NO analysis result according to an embodiment of the present invention. MCF7 cells were treated with 0.5 mg/ml soybean ferment extract for 1 day (0.5). Cells were placed in a NO fluorescence assay probe and stored for 1.5 h. Cell images (A) and (B) were obtained using a fluorescence microscope (DMi8, Leica) equipped with a FITC filter. The intensity of the cells was measured using the Image J program (C).
본 발명은 다양한 변환을 가할 수 있고 여러 가지 실시 예를 가질 수 있는 바, 특정 실시 예들을 상세한 설명에서 상세하게 설명하고자 한다. 그러나, 이는 본 발명을 특정한 실시 형태에 대해 한정하려는 것이 아니며, 본 발명의 사상 및 기술 범위에 포함되는 모든 변환, 균등물 내지 대체물을 포함하는 것으로 이해되어야 한다. 본 발명을 설명함에 있어서 관련된 공지 기술에 대한 구체적인 설명이 본 발명의 요지를 흐릴 수 있다고 판단되는 경우 그 상세한 설명을 생략한다.Since the present invention can apply various transformations and can have various embodiments, specific embodiments will be described in detail in the detailed description. However, this is not intended to limit the present invention to specific embodiments, and it should be understood to include all modifications, equivalents and substitutes included in the spirit and scope of the present invention. In describing the present invention, if it is determined that a detailed description of a related known technology may obscure the gist of the present invention, the detailed description thereof will be omitted.
이하, 도면들을 참조하여 본 발명의 실시예에 대해 상세히 설명하기로 한다. 본 발명은 본 발명의 정신 및 필수적 특징을 벗어나지 않는 범위에서 다른 특정한 형태로 구체화될 수 있음은 당업자에게 자명하다.Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings. It is apparent to those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit and essential characteristics of the present invention.
본 발명의 바람직한 일 실시예에 따른 유방암의 예방, 치료 또는 전이억제용 약학적 조성물은 PLAU(plasminogen activator, urokinase) 단백질 및 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제하는 대두 발효 추출물을 유효성분으로 포함한다.The pharmaceutical composition for preventing, treating or inhibiting metastasis of breast cancer according to a preferred embodiment of the present invention is a soybean fermented extract that inhibits the expression or activity of PLAU (plasminogen activator, urokinase) protein and ERBB2 (epidermal growth factor receptor 2) protein as an active ingredient.
상기 대두 발효 추출물은 Bacillus licheniformis 균주로 대두를 발효시킨 대두 발효물을 에탄올로 추출하여 제조된 청국장 추출물인 것을 특징으로 한다. The soybean fermented extract is characterized in that it is a cheonggukjang extract prepared by extracting the soybean fermented product obtained by fermenting soybeans with a Bacillus licheniformis strain with ethanol.
상기 Bacillus licheniformis 균주는 Bacillus licheniformis B1 균주인 것이 바람직하고, 본 발명의 실시예에서 사용한 상기 바실러스 리케니포미스(Bacillus licheniformis) B1은 본 발명자가 대한민국 특허출원 제2000-18724호로 특허출원하여 대한민국 특허등록 제0368183호로 특허받은 것에 따른 KCTC 0755BP 균주이다. The Bacillus licheniformis strain is preferably a Bacillus licheniformis B1 strain, and the Bacillus licheniformis B1 used in the examples of the present invention is a Korean patent application filed by the present inventor as Korean Patent Application No. 2000-18724 and registered as a Korean patent It is a KCTC 0755BP strain according to patent No. 0368183.
바람직하게는, 상기 대두 발효 추출물은 Ala-Phe-Pro-Gly, Gly-Val-Ala-Trp-Trp-Met-Tyr, Lys-Pro 및 Gln-Lys 으로 이루어진 군 중에서 1종 이상 선택되는 펩티드를 포함하는 것을 특징으로 한다.Preferably, the soybean ferment extract comprises at least one peptide selected from the group consisting of Ala-Phe-Pro-Gly, Gly-Val-Ala-Trp-Trp-Met-Tyr, Lys-Pro and Gln-Lys. characterized in that
본 발명의 다른 실시예에 따른 유방암의 예방, 치료 또는 전이억제용 약학적 조성물은 PLAU(plasminogen activator, urokinase) 단백질의 발현 또는 활성 억제제를 유효성분으로 포함한다. 상기 PLAU(plasminogen activator, urokinase) 단백질의 발현 또는 활성 억제제는 전술한 대두 발효 추출물이다.The pharmaceutical composition for preventing, treating or inhibiting metastasis of breast cancer according to another embodiment of the present invention includes an inhibitor of PLAU (plasminogen activator, urokinase) protein expression or activity as an active ingredient. The PLAU (plasminogen activator, urokinase) protein expression or activity inhibitor is the above-mentioned fermented soybean extract.
본 발명에서 용어, "유방암"은 유방에 생긴 암세포로 이루어진 종괴를 의미하며, 일반적으로는 유방의 유관과 소엽에서 발생한 암을 의미한다. 예컨대, 유방암은 생검(biopsy)에 의해 악성 병리상태로 분류되는 상태로, 유방암 진단의 임상적인 기술은 의학 분야에 잘 알려져 있다. 당업자라면 유방암이, 예컨대 악성 종양 및 육종을 포함한, 유방 조직의 모든 악성을 나타냄을 이해할 것이다. 예시적으로, 유방암은 유방내암(ductal carcinomain situ, DCIS), 상피내 소엽성 암종(lobular carcinoma in situ, LCIS), 점액성 유방암(mucinous carcinoma), 침윤성 관상피암(infiltrating ductal carcinoma, IDC), 침윤성 소엽내암(infiltrating lobular carcinoma,ILC) 등을 포함한다. As used herein, the term "breast cancer" refers to a mass consisting of cancer cells generated in the breast, and generally refers to cancer occurring in the ducts and lobules of the breast. For example, breast cancer is a condition classified as a malignant pathology by biopsy, and clinical techniques for diagnosing breast cancer are well known in the medical field. Those skilled in the art will understand that breast cancer represents all malignancies of breast tissue, including, for example, malignancies and sarcomas. Illustratively, the breast cancer is ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), mucinous carcinoma, infiltrating ductal carcinoma (IDC), invasive lobular carcinoma infiltrating lobular carcinoma (ILC) and the like.
본 발명에서 용어, "PLAU(plasminogen activator, urokinase)"는 플라스미노겐이 분해되어 생성된 플라스민의 활성화를 촉매하는 유로키나제(urokinase, uPA)를 말한다. As used herein, the term “plasminogen activator (urokinase)” refers to urokinase (uPA) that catalyzes the activation of plasmin produced by decomposition of plasminogen.
본 발명에서 용어, "ERBB2(epidermal growth factor receptor 2)"는 유방암 세포의 증식과 생존에 관계하는 중요한 신호전달 체계 중의 하나인 상피세포 성장인자수용체 (epidermal growth factor receptor; EGFR) 패밀리로서, HER2라고도 한다. EGFR 패밀리의 티로신 인산화효소 수용체(receptor tyrosine kinases)는 erb1, erb2/HER2, erb3, erb4의 4개로 되어 있으며 세포 증식(proliferation)과 생존(survival) 외에도 세포의 부착(adhesion), 이동(migration) 및 분화(differentiation)를 조절하는데 관여하는 것으로 알려져 있다. 4개의 erb family 중 erb2/HER2가 결합하는 리간드는 없지만 유방암에서 가장 강력한 암유전자(oncoprotein)로 알려져 있다. HER2가 정상적인 수준인 경우에는 정상적인 유선조직의 성장과 발달에 관여하지만, 비정상적으로 HER2가 과발현하거나 증폭되면 정상세포 조절이 붕괴되어 유선조직에서는 공격적인 암세포가 형성되게 된다. As used herein, the term "epidermal growth factor receptor 2 (ERBB2)" is an epidermal growth factor receptor (EGFR) family, which is one of the important signal transduction systems related to the proliferation and survival of breast cancer cells, and is also referred to as HER2. do. The EGFR family of tyrosine kinase receptors (receptor tyrosine kinases) is composed of four of erb1, erb2/HER2, erb3, and erb4. In addition to cell proliferation and survival, cell adhesion, migration and It is known to be involved in regulating differentiation. Although there is no erb2/HER2 binding ligand among the four erb families, it is known as the most potent oncoprotein in breast cancer. When HER2 is at a normal level, it is involved in the growth and development of normal mammary gland tissue, but when HER2 is abnormally overexpressed or amplified, normal cell regulation is disrupted, resulting in the formation of aggressive cancer cells in mammary gland tissue.
본 발명에서 용어 "전이 (metastasis)"는 악성 종양이 발병한 장기에서 떨어진 다른 조직으로 전파한 상태를 말한다. 하나의 장기에서 시작한 악성 종양이 진행함에 따라 처음 발생한 원발 부위인 장기로부터 다른 조직으로 퍼져 나가는데, 이렇게 원발 부위로부터 다른 조직으로 퍼져 나가는 것을 전이라 할 수 있다. 전이는 악성 종양의 진행에 수반되는 현상이라고 할 수 있는데, 악성 종양 세포가 증식하고 암이 진행함에 따라 새로운 유전 형질을 획득하면서 전이가 일어날 수 있다. 새로운 유전 형질을 획득한 종양 세포가 혈관과 림프선으로 침입하고 혈액과 림프를 따라 순환하다가 다른 조직에 정착, 증식하게 되면 전이가 일어날 수 있다. 전이가 발생하는 조직에 따라, 간암, 신장암, 폐암, 위암, 대장암, 직장암, 췌장암 등 각종 암질환이 유발될 수 있다. 본 발명의 조성물은 전이를 억제하여 암이 퍼지는 것을 예방 및 치료할 수 있다.In the present invention, the term “metastasis” refers to a state in which a malignant tumor has spread to other tissues away from the diseased organ. As a malignant tumor that starts in one organ progresses, it spreads from the primary site, the organ, to other tissues. Metastasis can be said to be a phenomenon accompanying the progression of malignant tumors, and metastases can occur while malignant tumor cells proliferate and acquire new genetic traits as the cancer progresses. When tumor cells that have acquired new genetic traits invade into blood vessels and lymph glands, circulate through blood and lymph, and settle and proliferate in other tissues, metastasis can occur. Depending on the tissue in which metastasis occurs, various cancer diseases such as liver cancer, kidney cancer, lung cancer, stomach cancer, colorectal cancer, rectal cancer, and pancreatic cancer may be induced. The composition of the present invention can prevent and treat the spread of cancer by inhibiting metastasis.
본 발명에서 용어, "억제"는 본 발명에 따른 조성물의 투여로 PLAU(plasminogen activator, urokinase) 단백질 또는 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제시키고, 유방암 세포의 성장 억제 및 상기 유방암의 전이를 억제시키는 모든 행위를 말한다.As used herein, the term "inhibition" refers to the administration of the composition according to the present invention to inhibit the expression or activity of PLAU (plasminogen activator, urokinase) protein or ERBB2 (epidermal growth factor receptor 2) protein, and inhibit the growth of breast cancer cells and the It refers to any action that inhibits the metastasis of breast cancer.
본 발명의 구체적인 일 실시예에서는 유방암세포를 청국장 추출물로 처리하고 PLAU와 ERBB2 발현정도를 측정한 결과, 청국장 추출물이 PLAU와 ERBB2 발현을 상당히 억제한다는 것을 확인하였다(도 2). In a specific embodiment of the present invention, as a result of treating breast cancer cells with cheonggukjang extract and measuring the expression level of PLAU and ERBB2, it was confirmed that the chungkukjang extract significantly inhibited PLAU and ERBB2 expression (FIG. 2).
즉, 본 발명의 실시예에 따르면, 발효대두 청국장에는 대두단백질이 발효에 의해 분해 형성된 다양한 펩타이드류가 들어 있고, 이러한 청국장 추출물이 처리된 유방암세포의 microarray data와 잘 알려진 유방암 전이 마커를 합쳐서 새로운 연결망이 제조되었으며 이를 이용해 전이 마커와 발현 차이가 있는 단백질 사이의 상호작용을 체크하였다. 이러한 연결망 분석을 통해 PLAU (plasminogen activator, urokinase, uPA)와 ERBB2 (epidermal growth factor receptor 2)를 실제 전이 가능성을 보여주는 유전자로 선택하였고, MCF7 암세포를 청국장추출물로 처리하고 PLAU와 ERBB2 발현정도를 측정한 결과, 청국장 추출물이 PLAU와 ERBB2 발현을 억제하였다. That is, according to an embodiment of the present invention, fermented soybean cheonggukjang contains various peptides formed by decomposition of soybean protein by fermentation, and microarray data of breast cancer cells treated with this cheonggukjang extract and well-known breast cancer metastasis markers are combined to create a new network. was prepared, and the interaction between the metastasis marker and the protein with different expression was checked. Through this network analysis, PLAU (plasminogen activator, urokinase, uPA) and ERBB2 (epidermal growth factor receptor 2) were selected as genes showing actual metastasis potential. As a result, cheonggukjang extract inhibited PLAU and ERBB2 expression.
본 발명의 다른 구체적인 일 실시예에서는 청국장 추출물을 처리한 유방암세포에서 염증 마커인 NO의 생산이 감소하였음을 확인하였다(도 3).In another specific embodiment of the present invention, it was confirmed that the production of NO, an inflammatory marker, was reduced in breast cancer cells treated with cheonggukjang extract (FIG. 3).
이에, 본 발명자들은 상기 결과를 통해 청국장 추출물이 유방암세포의 PLAU와 ERBB2의 발현을 상당히 억제한다는 것을 확인하였다.Accordingly, the present inventors confirmed that the cheonggukjang extract significantly inhibits the expression of PLAU and ERBB2 in breast cancer cells through the above results.
본 발명의 약학 조성물은 약학 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 또는 희석제를 추가로 포함할 수 있다. 약학적으로 허용 가능한 담체를 포함하는 조성물은 경구 또는 비경구의 여러 가지 제형일 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구 투여를 위한 고형제제에는 정제환제, 산제, 과립제, 캡슐제 등이 포함될 수 있으며, 이러한 고형제제는 하나 이상의 화합물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제들도 사용될 수 있다. 경구 투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함될 수 있다. 비수성용제, 현탁용제로는 프로필렌글리콜 (propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테로 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.The pharmaceutical composition of the present invention may further include an appropriate carrier, excipient or diluent commonly used in the preparation of pharmaceutical compositions. The composition comprising a pharmaceutically acceptable carrier may be in various oral or parenteral formulations. In the case of formulation, it can be prepared using a diluent or excipient such as a filler, extender, binder, wetting agent, disintegrant, surfactant, etc. commonly used. Solid preparations for oral administration may include tablet pills, powders, granules, capsules, etc., and such solid preparations may include one or more compounds and at least one excipient, for example, starch, calcium carbonate, sucrose or lactose. (lactose), gelatin, etc. can be mixed and prepared. In addition to simple excipients, lubricants such as magnesium stearate, talc and the like may also be used. Liquid formulations for oral administration include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. may be included. there is. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.
또한, 본 발명의 약학 조성물은 이에 제한되지는 않으나, 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제 및 좌제로 이루어진 군으로부터 선택되는 어느 하나의 제형을 가질 수 있다.In addition, the pharmaceutical composition of the present invention is not limited thereto, but tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations And it may have any one formulation selected from the group consisting of suppositories.
본 발명에서 용어, "치료"는 치료하고자 하는 개개인 또는 세포의 천연 과정을 변경시키기 위해 임상적으로 개입하는 것을 지칭하고, 이는 임상 병리 상태가 진행되는 동안 또는 이를 예방하기 위해 수행할 수 있다. 목적하는 치료 효과에는 질병의 발생 또는 재발을 예방하고, 증상을 완화시키며, 질병에 따른 모든 직접 또는 간접적인 병리학적 결과를 저하시키며, 전이를 예방하고, 질병 진행 속도를 감소시키며, 질병 상태를 경감 또는 일시적 완화시키며, 차도시키거나 예후를 개선시키는 것이 포함된다. 또한, "예방"은 본 발명에 따른 조성물의 투여로 상기 암의 발병을 억제 또는 지연시키는 모든 행위를 말한다.As used herein, the term "treatment" refers to clinical intervention to alter the natural process of an individual or cell to be treated, which can be performed during the progression of a clinical pathology or to prevent it. The desired therapeutic effect includes preventing the occurrence or recurrence of a disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, and alleviating the disease state. or temporary relief, remission or improvement of prognosis. In addition, "prevention" refers to any action that inhibits or delays the onset of the cancer by administration of the composition according to the present invention.
본 발명의 대두 발효 추출물을 유효성분으로 포함하는 조성물은 PLAU(plasminogen activator, urokinase) 단백질 및 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제하는 효과가 있으므로 유방암의 예방, 치료 또는 전이억제용 조성물로 우수한 효과가 있다.The composition comprising the fermented soybean extract of the present invention as an active ingredient has an effect of inhibiting the expression or activity of PLAU (plasminogen activator, urokinase) protein and ERBB2 (epidermal growth factor receptor 2) protein, so that breast cancer prevention, treatment or metastasis inhibition It has an excellent effect as a composition for use.
또한, 본 발명의 조성물은 PLAU(plasminogen activator, urokinase) 단백질의 발현 또는 활성 억제제를 유효성분으로 포함하여 유방암의 예방, 치료 또는 전이억제용 조성물로 우수한 효과가 있다.In addition, the composition of the present invention contains a PLAU (plasminogen activator, urokinase) protein expression or activity inhibitor as an active ingredient, and has an excellent effect as a composition for preventing, treating or inhibiting metastasis of breast cancer.
본 발명의 다른 실시예에 따른 유방암의 예방, 개선 또는 전이억제용 식품 조성물은 PLAU(plasminogen activator, urokinase) 단백질 및 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제하는 대두 발효 추출물을 유효성분으로 포함한다.The food composition for preventing, improving, or inhibiting metastasis of breast cancer according to another embodiment of the present invention is an effective soybean fermented extract that inhibits the expression or activity of PLAU (plasminogen activator, urokinase) protein and ERBB2 (epidermal growth factor receptor 2) protein. included as an ingredient.
상기 대두 발효 추출물은 전술한 바와 같이 Bacillus licheniformis 균주로 대두를 발효시킨 대두 발효물을 에탄올로 추출하여 제조된 청국장 추출물인 것을 특징으로 한다.The fermented soybean extract is characterized in that it is a cheonggukjang extract prepared by extracting the soybean fermented product obtained by fermenting soybeans with a Bacillus licheniformis strain with ethanol as described above.
본 발명에서 용어, "개선"은 대두 발효 추출물을 유효성분으로 포함하는 조성물을 이용하여 PLAU(plasminogen activator, urokinase) 단백질 및 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제하여 상기 질환의 의심 및 발병 개체의 증상이 호전되거나 이롭게 되는 모든 행위를 말한다.As used herein, the term "improvement" refers to the treatment of the disease by inhibiting the expression or activity of PLAU (plasminogen activator, urokinase) protein and ERBB2 (epidermal growth factor receptor 2) protein using a composition containing fermented soybean extract as an active ingredient. It refers to any action that improves or benefits the symptoms of the suspected or affected individual.
상기 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 천연 과일쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 추출물을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다.The food composition includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids , protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, it may contain extracts for the preparation of natural fruit juices and fruit juice beverages and vegetable beverages. These components may be used independently or in combination.
또한, 상기 식품 조성물은 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 껌류, 아이스크림류, 스프, 음료수, 차, 기능수, 드링크제, 알코올 음료 및 비타민 복합제 중 어느 하나의 형태일 수 있다.In addition, the food composition is in the form of any one of meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, drink, alcoholic beverage, and vitamin complex can be
본 발명의 다른 실시예는 PLAU(plasminogen activator, urokinase) 단백질 및 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제하는 대두 발효 추출물을 인간을 제외한 개체에 투여하는 단계를 포함하는 유방암의 치료 또는 전이 억제 방법이다.Another embodiment of the present invention relates to the treatment of breast cancer comprising administering to a subject other than a human a fermented soybean extract that inhibits the expression or activity of a plasminogen activator (urokinase) protein and an epidermal growth factor receptor 2 (ERBB2) protein or a method for inhibiting metastasis.
본 발명에서 용어, "개체"는 본 발명의 암 질환을 보유하거나 또는 발병한, 인간을 포함한 모든 동물을 의미하며, 인간을 제외한 개체일 수 있다. 본 발명의 약학 조성물을 개체에 투여함으로써, 간암을 비롯한 암의 전이를 억제할 수 있다.As used herein, the term “individual” refers to all animals, including humans, that have or have developed the cancer disease of the present invention, and may be individuals other than humans. By administering the pharmaceutical composition of the present invention to an individual, metastasis of cancer including liver cancer can be inhibited.
상기 본 발명의 약학 조성물은 약학적으로 유효한 양으로 투여한다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.
본 발명에서 용어, "투여"는 어떠한 적절한 방법으로 대상에게 본 발명의 약학 조성물을 도입하는 것을 말하며, 투여 경로는 목적 조직에 도달할 수 있는 한 경구 또는 비경구의 다양한 경로를 통하여 투여될 수 있다.As used herein, the term "administration" refers to introducing the pharmaceutical composition of the present invention to a subject by any suitable method, and the administration route may be administered through various routes, either oral or parenteral, as long as it can reach the target tissue.
상기 약학 조성물은 목적 또는 필요에 따라 당업계에서 사용되는 통상적인 방법, 투여 경로, 투여량에 따라 적절하게 개체에 투여될 수 있다. 투여 경로의 예로는 경구, 비경구, 피하, 복강 내, 폐 내, 및 비강 내로 투여될 수 있으며, 비경구 주입에는 근육 내, 정맥 내, 동맥 내, 복강 내 또는 피하투여가 포함된다. 또한 당업계에 공지된 방법에 따라 적절한 투여량 및 투여 횟수가 선택될 수 있으며, 실제로 투여되는 본 발명의 약학 조성물의 양 및 투여 횟수는 치료하고자 하는 증상의 종류, 투여 경로, 성별, 건강 상태, 식이, 개체의 연령 및 체중, 및 질환의 중증도와 같은 다양한 인자에 의해 적절하게 결정될 수 있다.The pharmaceutical composition may be appropriately administered to a subject according to a conventional method, administration route, and dosage used in the art, depending on the purpose or necessity. Examples of the route of administration may be oral, parenteral, subcutaneous, intraperitoneal, intrapulmonary, and intranasal administration, and parenteral injection includes intramuscular, intravenous, intraarterial, intraperitoneal or subcutaneous administration. In addition, an appropriate dosage and frequency of administration may be selected according to methods known in the art, and the amount and frequency of administration of the pharmaceutical composition of the present invention actually administered depends on the type of symptom to be treated, administration route, sex, health status, It can be appropriately determined by various factors such as diet, the age and weight of the individual, and the severity of the disease.
본 발명에서의 용어 "약학적으로 유효한 양"은 의학적 용도에 적용 가능한 합리적인 수혜/위험 비율로 혈관 투과성 증가를 억제 또는 완화하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다. 그리고 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다.As used herein, the term “pharmaceutically effective amount” means an amount sufficient to inhibit or alleviate an increase in vascular permeability at a reasonable benefit/risk ratio applicable to medical use, and the effective dose level may vary depending on the type and severity of the subject, age, It can be determined according to factors including sex, drug activity, drug sensitivity, administration time, administration route and excretion rate, duration of treatment, co-administered drugs, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. and may be administered single or multiple. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, and can be easily determined by those skilled in the art.
이하, 실시예를 통하여 본 발명을 더욱 상세하게 설명하고자 하나, 하기의 실시예는 단지 설명의 목적을 위한 것이며, 본 발명의 범위를 한정하고자 하는 것은 아니다.Hereinafter, the present invention will be described in more detail through examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.
실시예 1: 유방암 세포주 및 대두 발효 추출물 처리Example 1: Treatment of breast cancer cell line and soybean ferment extract
대두 발효 추출물에 대한 마이크로어레이 분석 결과에 기반하여 상이하게 발현된 유전자들 및 공지된 유방암 전이 마커들인 ERBB2, MMP1, MMP9, CD9, ADAM9 및 BCL2을 모두 포함한 이들 간의 상호 작용을 확인하기 위하여 새로운 연결망(네트워크) 분석을 진행하였다. Based on the results of microarray analysis of soybean ferment extract, a novel network ( network) analysis was performed.
MCF7 세포를 DMEM 배지(Dulbecco’s Modification of Eagle’s medium, Cornig)에 10% 소 태아 혈청(Fetal Bovine Serum), 1% 항생제-항균제(Caisson), 및 대두 발효 추출물을 첨가하여 37°C, 5% CO2 하에서 배양하였다. 대두는 Bacillus licheniformis B1으로 발효시키고, 발효된 대두를 에탄올로 추출하여 대두 발효 추출물을 제조하였다. 대두를 발효한 청국장은 발효 과정 중 대두 단백질의 분해로 생성된 다양한 올리고 펩타이드들이 풍부하게 존재하며, 상기 펩타이드들은 세포 신호 전달에 있어서 중심적 역할을 한다. Bacillus licheniformis B1에 의해 발효된 대두 단백질 유래 펩타이드들은 Ala-Phe-Pro-Gly, Gly-Val-Ala-Trp-Trp-Met-Tyr, Lys-Pro 및 Gln-Lys 등이 있다.MCF7 cells were cultured in DMEM medium (Dulbecco's Modification of Eagle's medium, Cornig) by adding 10% Fetal Bovine Serum, 1% antibiotic-antibacterial agent (Caisson), and soybean ferment extract under 37°C, 5% CO2. cultured. Soybeans were fermented with Bacillus licheniformis B1, and the fermented soybeans were extracted with ethanol to prepare a soybean fermented extract. Cheonggukjang fermented soybean is rich in various oligopeptides produced by the degradation of soybean protein during the fermentation process, and the peptides play a central role in cell signal transduction. Peptides derived from soy protein fermented by Bacillus licheniformis B1 include Ala-Phe-Pro-Gly, Gly-Val-Ala-Trp-Trp-Met-Tyr, Lys-Pro and Gln-Lys.
RNA 프렙(prep) 키트(GeneAll)를 사용하여 RNA를 정제하였다. 0.2 mM dNTP 각각, 0.01 μmol 올리고(oligo) dT, 350 ng RNA 템플레이트(template), 1 유닛(unit) 알엔나제(Rnase) 억제제를 70 ℃에서 10 분간 반응시켰다.RNA was purified using an RNA prep kit (GeneAll). Each 0.2 mM dNTP, 0.01 μmol oligo dT, 350 ng RNA template, and 1 unit Rnase inhibitor were reacted at 70° C. for 10 minutes.
cDNA 합성을 위하여 2 μl RT 완충액, 10 유닛 역전사 효소(Enzynomics)를 혼합물에 첨가하고, 43 ℃에서 90 분 및 70 ℃에서 5 분간 반응시켰다. 정량적 RT PCR이 2X quanti Mix SYBR (Illumina)을 사용하여 수행되었다.For cDNA synthesis, 2 μl RT buffer and 10 units of reverse transcriptase (Enzynomics) were added to the mixture, and reacted at 43° C. for 90 minutes and 70° C. for 5 minutes. Quantitative RT PCR was performed using 2X quanti Mix SYBR (Illumina).
PLAU 프라이머 시퀀스(primer sequences); A:5'-TCACCACCAAAATGCTGTGT-3'(서열번호 1), B: 5'-AGGCCATTCTCTCTTCCTTGGT-3'(서열번호 2), β-actin A: 5'-CGACTTCGAGCAAGAGATGG-3'(서열번호 3), and B:5'-AGCACTGTGTTGGCGTACAG-3'(서열번호 4).PAU primer sequences; A:5'-TCACCACCAAAATGCTGTGT-3' (SEQ ID NO: 1), B: 5'-AGGCCATTCTCTCTTCCTTGGT-3' (SEQ ID NO: 2), β-actin A: 5'-CGACTTCGAGCAAGAGATGG-3' (SEQ ID NO: 3), and B :5'-AGCACTGTGTTGGCGTACAG-3' (SEQ ID NO: 4).
PCR 30사이클(95°C에서 15 초간, 55°C에서 30 초간)이 수행되었다.30 cycles of PCR (15 s at 95 °C and 30 s at 55 °C) were performed.
ERBB2 프라이머 시퀀스(primer sequences); A: 5'-CAGCCTTGCCCCATCAAC-3'(서열번호 5), B: 5'-GCCCTTGTCATCCAGGTCC-3'(서열번호 6). β-actin A:5'-CGACTTCGAGCAAGAGATGG-3'(서열번호 3), and B: 5'-AGCACTGTGTTGGCGTACAG-3'(서열번호 4). ERBB2 primer sequences; A: 5'-CAGCCTTGCCCCATCAAC-3' (SEQ ID NO: 5), B: 5'-GCCCTTGTCATCCAGGTCC-3' (SEQ ID NO: 6). β-actin A:5'-CGACTTCGAGCAAGAGATGG-3' (SEQ ID NO: 3), and B: 5'-AGCACTGTGTTGGCGTACAG-3' (SEQ ID NO: 4).
PCR 30사이클(95°C에서 15 초간, 55°C에서 30 초간)이 수행되었다.30 cycles of PCR (15 s at 95 °C and 30 s at 55 °C) were performed.
MCF7 세포를 0.5 mg/ml 대두 발효 추출물로 1 일 동안 처리하였다. 세포를 NO 형광분석 프로브에 넣고 1.5 시간 동안 저장하였다. 세포 이미지는 FITC 필터가 장착된 형광현미경(DMi8, Leica)을 이용하여 얻었다. 세포의 형광 강도는 Image J 프로그램(국립 보건원)을 사용하여 결정되었다.MCF7 cells were treated with 0.5 mg/ml soybean ferment extract for 1 day. Cells were placed in a NO fluorescence probe and stored for 1.5 h. Cell images were obtained using a fluorescence microscope (DMi8, Leica) equipped with a FITC filter. The fluorescence intensity of the cells was determined using the Image J program (National Institute of Health).
단백질 - 단백질 상호 작용(PPI) 연결망(네트워크)을 공지의 PPI 데이터베이스를 스캔하여 구축하였다. PPI 데이터를 휴먼 프로틴 레퍼런스 데이터베이스(Human Protein Reference Database, HPRD, http : //www.hprd.org/)에서 다운로드하였다. 상호 작용하는 단백질 쌍(pairs)은 SQLite3 데이터베이스 엔진 (https://www.sqlite.org/)에 저장되었다. 파이썬(Phthon, https://www.python.org/) 구동 스크립트를 사용하여 SQLite3 데이터베이스와 인터페이스하여 PPI 데이터를 검사하였다. Protein-protein interaction (PPI) networks (networks) were constructed by scanning known PPI databases. PPI data were downloaded from the Human Protein Reference Database (HPRD, http://www.hprd.org/). The interacting protein pairs were stored in the SQLite3 database engine (https://www.sqlite.org/). A Python (Phthon, https://www.python.org/) startup script was used to interface with the SQLite3 database to examine the PPI data.
문헌 조사 및 마이크로어레이 분석에 의하여 선택된 단백질들을 스캔닝을 위한 입력값으로 사용하였다. 만약 하나의 PPI 쌍이 하나의 입력 단백질을 포함한다면 그 상호 작용은 상기 연결망(네트워크)에 포함된다. 상기 상호 작용들이 중복될 경우는 무시된다. 단일 종단의 입력 및 출력 노드를 제거하여 단순화된 연결망(네트워크)의 핵심 사항을 획득하였다(Kim et al., 2011). 상기 상호 작용을 포함하는 그래프를 시각화하고 Cytoscape 프로그램(http://www.cytoscape.org/)을 사용하여 수동으로 편집하였다.Proteins selected by literature search and microarray analysis were used as input for scanning. If one PPI pair contains one input protein, the interaction is included in the network (network). If the above interactions overlap, they are ignored. By removing single-ended input and output nodes, the core of a simplified network (network) was obtained (Kim et al., 2011). Graphs containing the interactions were visualized and manually edited using the Cytoscape program (http://www.cytoscape.org/).
유방암 MCF7 세포를 대두 발효 추출물로 처리한 후 유의미하게 상이한 수준으로 발현하는 91개의 유전자 리스트를 이전의 연구에서 얻었다((황 외., 2011). 그리고, 전이 핵심 마커로는 ERBB2, MMP1, MMP9, CD9, ADAM9 및 BCL2가 있다. 전이 마커 단백질과 상이하게 발현된 유전자들 간의 상호 작용이 컴바인된 연결망(네트워크)에 확인할 수 있다. 도 1은 컴바인되고 단순화된 연결망(네트워크)을 도시하고 있다.A list of 91 genes expressing significantly different levels of breast cancer MCF7 cells after treatment with soybean ferment extract was obtained in a previous study ((Hwang et al., 2011). And, as key metastasis markers, ERBB2, MMP1, MMP9, CD9, ADAM9 and BCL2.The interaction between the metastasis marker protein and the differentially expressed genes can be confirmed in the combined network (network) Fig. 1 shows the combined and simplified network (network).
마이크로 어레이 분석에 있어서 상기 처리후 CASP3 및 PLAU와 같은 암 전이 마커의 유전자 발현 수준이 각각 1.4 배 및 1.3 배 감소하였다(황 외., 2011). CASP3은 연결망(네트워크) 상의 CTNNB1과 KPNB1을 통해 ERBB2와의 상호 작용을 나타낸다(도 1). In microarray analysis, the gene expression levels of cancer metastasis markers such as CASP3 and PLAU decreased by 1.4-fold and 1.3-fold, respectively, after the treatment (Hwang et al., 2011). CASP3 represents the interaction with ERBB2 through CTNNB1 and KPNB1 on the connection network (network) (FIG. 1).
CASP3 및 PLAU 발현의 감소가 전이 과정을 방해할 것으로 예상한다. 몇몇의 단백질들은 단지 마이크로어레이 단백질들만으로 구성된 단백질 상호 연결망(네트워크)에서 유의미한 기능을 나타내지 못 하였다. 그러나, 전이 마커를 포함하는 통합된 상호 연결망(네트워크)은 새로운 단백질 상호작용을 제시하였다. -1.4 배 발현을 보인 CXCL2은 PLG를 통해 MMP9와 상호 작용을 하였다(도 1). CCL3는 MMP 관련 단백질과의 상호 작용에서 중심 역할을 했다(도 1). It is expected that the reduction of CASP3 and PLAU expression will interfere with the metastatic process. Some proteins did not show a significant function in the protein interconnection network (network) composed of only microarray proteins. However, integrated interconnections (networks) containing metastatic markers have suggested novel protein interactions. CXCL2, which showed -1.4 fold expression, interacted with MMP9 through PLG (Fig. 1). CCL3 played a central role in the interaction with MMP-related proteins (Fig. 1).
실시예 2: PLAU 및 ERBB2의 발현 억제Example 2: Inhibition of expression of PLAU and ERBB2
암 세포 침습(invasion)은 세포외기질(extracellular matrix, ECM)을 분해하여 달성된다. uPA는 암세포를 분리하여 다른 사이트로의 이동을 유도하는데 관련된다. uPA는 많은 암세포에서 과다 발현되고 전이 과정에서 결정적인 역할을 한다. uPA 과발현은 유방암 및 전이 과정의 좋지 않은 결과와 관련되어 있다(Foekens et al., 2000; Egeblad and Werb, 2002; Vizoso et al., 2007). uPA는 암 줄기세포능(cancer stemness)을 촉진하기 위하여 전사 인자와 상호 작용한다. uPA에 의한 전사 조절은 암 줄기세포능 및 임상적 치사율에 기여한다. 췌장관세포암(PDAC, Pancreatic ductal adenocarcinoma)의 치사는 암줄기세포(cancer stem cell)와 관련이 있다. PDAC의 나쁜 예후는 uPA의 증가된 발현과 관련이 있다. 여기서, 암줄기세포란, 암세포 내에 암을 촉발시키는 시원세포를 의미하는데, 암세포와는 별도로 존재하고, 정상 줄기세포의 특성을 갖고 있는 것으로 알려져 있다.Cancer cell invasion is achieved by breaking down the extracellular matrix (ECM). uPA is involved in isolating cancer cells and inducing migration to other sites. uPA is overexpressed in many cancer cells and plays a crucial role in the metastasis process. uPA overexpression has been associated with poor outcomes in breast cancer and metastatic processes (Foekens et al., 2000; Egeblad and Werb, 2002; Vizoso et al., 2007). uPA interacts with transcription factors to promote cancer stemness. Transcriptional regulation by uPA contributes to cancer stem cell capacity and clinical mortality. The lethality of pancreatic ductal adenocarcinoma (PDAC) is associated with cancer stem cells. The poor prognosis of PDAC is associated with increased expression of uPA. Here, the cancer stem cells, which refer to primitive cells that trigger cancer in cancer cells, exist separately from cancer cells and are known to have characteristics of normal stem cells.
ERBB2는 상피 성장 인자 수용체(epidermal growth factor receptors, EGFR)를 포함하는 티로신 키나아제 패밀리 중 하나이다. NSLC(None small cell Lung Cancer) 세포 및 유방암 세포는 EGFR의 변이형을 가지고 있거나 과잉 생산되어 있다(Li et al., 2008; Chuang et al., 2017). ERBB2 is one of a family of tyrosine kinases that includes epidermal growth factor receptors (EGFR). Non small cell lung cancer (NSLC) cells and breast cancer cells have EGFR variants or are overproduced (Li et al., 2008; Chuang et al., 2017).
본 발명자들은 유방암 MCF7 세포를 대두 발효 추출물을 처리하고, PLAU 및 ERBB2의 발현 수준을 측정하였다. 놀랍게도, 대두 발효 추출물은 PLAU 및 ERBB2의 발현을 억제하였다(도 2). B. licheniformis B1에 의해 발효된 상기 대두 발효 추출물의 특정 펩타이드들이 PLAU 및 ERBB2의 발현을 억제하는 것으로 보인다.The present inventors treated breast cancer MCF7 cells with fermented soybean extract and measured the expression levels of PLAU and ERBB2. Surprisingly, the soybean ferment extract inhibited the expression of PLAU and ERBB2 (Fig. 2). Certain peptides of the soybean ferment extract fermented by B. licheniformis B1 appear to inhibit the expression of PLAU and ERBB2.
실시예 3: NO 분석Example 3: NO Analysis
염증은 전이와 관련된다. 대두 발효 추출물은 전이와 관련된 유전자 발현을 억제하였으므로, 유방암 세포에서 염증 표지자 NO의 생성에 대두 발효 추출물의 영향을 분석하였다. 대두 발효 추출물로 처리한 암 세포에서 NO 생성은 현저하게 감소하였다(도 3).Inflammation is associated with metastasis. Since the soybean fermented extract inhibited metastasis-related gene expression, the effect of the soybean fermented extract on the production of the inflammatory marker NO in breast cancer cells was analyzed. NO production was significantly reduced in cancer cells treated with soybean ferment extract ( FIG. 3 ).
한편, 이상의 상세한 설명은 모든 면에서 제한적으로 해석되어서는 아니되고 예시적인 것으로 고려되어야 한다. 본 발명의 범위는 첨부된 청구항의 합리적 해석에 의해 결정되어야 하고, 본 발명의 등가적 범위 내에서의 모든 변경은 본 발명의 범위에 포함된다.On the other hand, the above detailed description should not be construed as restrictive in all aspects, but should be considered as exemplary. The scope of the present invention should be determined by a reasonable interpretation of the appended claims, and all modifications within the equivalent scope of the present invention are included in the scope of the present invention.
Claims (9)
상기 연결망을 통해 PLAU (plasminogen activator, urokinase, uPA)와 ERBB2 (epidermal growth factor receptor 2)를 유방암 세포의 예방, 치료 또는 전이 억제 관련 후보 단백질로 선택하는 단계;
를 포함하는 유방암 세포의 예방, 치료 또는 전이 억제 관련 후보 단백질을 스크리닝하는 방법.
Conducting a network analysis for the protein-protein interaction (PPI) between the expressed protein and the known breast cancer metastasis protein based on the microarray analysis result of the cheonggukjang extract for breast cancer cells; and
selecting PLAU (plasminogen activator, urokinase, uPA) and ERBB2 (epidermal growth factor receptor 2) as candidate proteins related to prevention, treatment, or metastasis inhibition of breast cancer cells through the network;
A method of screening a candidate protein related to prevention, treatment or metastasis inhibition of breast cancer cells comprising a.
상기 청국장 추출물은 Bacillus licheniformis 균주로 대두를 발효시킨 추출물인 것을 특징으로 하는 유방암 세포의 예방, 치료 또는 전이 억제 관련 후보 단백질을 스크리닝하는 방법.
According to claim 1,
The method for screening a candidate protein related to prevention, treatment or metastasis inhibition of breast cancer cells, characterized in that the cheonggukjang extract is an extract obtained by fermenting soybeans with a Bacillus licheniformis strain.
상기 청국장 추출물은 Bacillus licheniformis 균주로 대두를 발효시킨 대두 발효물을 에탄올로 추출하여 제조된 추출물인 것을 특징으로 하는 유방암 세포의 예방, 치료 또는 전이 억제 관련 후보 단백질을 스크리닝하는 방법.
According to claim 1,
The method for screening a candidate protein related to prevention, treatment or metastasis inhibition of breast cancer cells, characterized in that the cheonggukjang extract is an extract prepared by extracting a soybean fermented product obtained by fermenting soybeans with a Bacillus licheniformis strain with ethanol.
상기 연결망을 통해 PLAU (plasminogen activator, urokinase, uPA)와 ERBB2 (epidermal growth factor receptor 2)를 유방암 세포의 예방, 치료 또는 전이 억제 관련 후보 단백질로 선택하는 단계; 및
상기 유방암 세포의 예방, 치료 또는 전이 억제 관련 후보 단백질로 선택된 PLAU 및 ERBB2의 발현 또는 활성을 억제시키기 위하여 상기 청국장 추출물을 유방암 세포에 처리하는 단계;
를 포함하는 것을 특징으로 하는 인간을 제외한 동물의 유방암 세포에서 PLAU(plasminogen activator, urokinase) 단백질 및 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제시키는 방법.
Conducting a network analysis for the protein-protein interaction (PPI) between the expressed protein and the known breast cancer metastasis protein based on the microarray analysis result of the cheonggukjang extract for breast cancer cells; and
selecting PLAU (plasminogen activator, urokinase, uPA) and ERBB2 (epidermal growth factor receptor 2) as candidate proteins related to prevention, treatment, or metastasis inhibition of breast cancer cells through the network; and
treating the breast cancer cells with the cheonggukjang extract in order to inhibit the expression or activity of PLAU and ERBB2 selected as candidate proteins related to the prevention, treatment or metastasis inhibition of the breast cancer cells;
A method of inhibiting the expression or activity of PLAU (plasminogen activator, urokinase) protein and ERBB2 (epidermal growth factor receptor 2) protein in breast cancer cells of animals other than humans, comprising a.
상기 청국장 추출물은 Bacillus licheniformis 균주로 대두를 발효시킨 추출물인 것을 특징으로 하는 인간을 제외한 동물의 유방암 세포에서 PLAU(plasminogen activator, urokinase) 단백질 및 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제시키는 방법.
5. The method of claim 4,
The cheonggukjang extract inhibits the expression or activity of PLAU (plasminogen activator, urokinase) protein and ERBB2 (epidermal growth factor receptor 2) protein in breast cancer cells of animals other than humans, characterized in that it is an extract obtained by fermenting soybeans with a Bacillus licheniformis strain. how to do it.
상기 청국장 추출물은 Bacillus licheniformis 균주로 대두를 발효시킨 대두 발효물을 에탄올로 추출하여 제조된 추출물인 것을 특징으로 하는 인간을 제외한 동물의 유방암 세포에서 PLAU(plasminogen activator, urokinase) 단백질 및 ERBB2(epidermal growth factor receptor 2) 단백질의 발현 또는 활성을 억제시키는 방법.5. The method of claim 4,
The cheonggukjang extract is PLAU (plasminogen activator, urokinase) protein and ERBB2 (epidermal growth factor) in breast cancer cells of animals other than humans, characterized in that it is an extract prepared by extracting a soybean fermented product obtained by fermenting soybeans with a Bacillus licheniformis strain with ethanol. receptor 2) A method of inhibiting the expression or activity of a protein.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020190065726A KR102283767B1 (en) | 2019-06-04 | 2019-06-04 | Pharmaceutical composition for preventing, treating and inhibiting metastasis of breast cancer comprising fermented soybean extract suppressing PLAU and ERBB2 expressions |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020190065726A KR102283767B1 (en) | 2019-06-04 | 2019-06-04 | Pharmaceutical composition for preventing, treating and inhibiting metastasis of breast cancer comprising fermented soybean extract suppressing PLAU and ERBB2 expressions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20200139350A KR20200139350A (en) | 2020-12-14 |
| KR102283767B1 true KR102283767B1 (en) | 2021-08-02 |
Family
ID=73779939
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020190065726A KR102283767B1 (en) | 2019-06-04 | 2019-06-04 | Pharmaceutical composition for preventing, treating and inhibiting metastasis of breast cancer comprising fermented soybean extract suppressing PLAU and ERBB2 expressions |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR102283767B1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030008023A1 (en) | 2001-03-21 | 2003-01-09 | Kung-Ming Lu | Methods for inhibiting cancer growth, reducing infection and promoting general health with a fermented soy extract |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100909998B1 (en) | 2007-03-29 | 2009-07-29 | 주식회사 인섹트 바이오텍 | Pharmaceutical composition for breast cancer prevention and treatment with arazyme as an active ingredient |
-
2019
- 2019-06-04 KR KR1020190065726A patent/KR102283767B1/en active IP Right Grant
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030008023A1 (en) | 2001-03-21 | 2003-01-09 | Kung-Ming Lu | Methods for inhibiting cancer growth, reducing infection and promoting general health with a fermented soy extract |
Non-Patent Citations (1)
| Title |
|---|
| 호서대학교대학원. 석사학위논문. 송혜정. (2011.02.)* |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20200139350A (en) | 2020-12-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Costa et al. | Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers | |
| Fasanella et al. | Pain in chronic pancreatitis and pancreatic cancer | |
| Molloy et al. | Extra-abdominal desmoid tumours: a review of the literature | |
| Mahadevan et al. | Novel receptor tyrosine kinase targeted combination therapies for imatinib-resistant gastrointestinal stromal tumors (GIST) | |
| CN107095867B (en) | Application of HSP90 inhibitor in preparation of medicine for preventing and treating aortic disease | |
| WO2019111998A1 (en) | Cancer spheroid production method and method for selecting colon cancer patients | |
| WO2019216360A1 (en) | Prophylactic or therapeutic agent for prostate cancer | |
| KR102283767B1 (en) | Pharmaceutical composition for preventing, treating and inhibiting metastasis of breast cancer comprising fermented soybean extract suppressing PLAU and ERBB2 expressions | |
| CN112867495A (en) | Gastric cancer therapeutic composition comprising SYT11 inhibitor as active ingredient | |
| Wu et al. | Tyrosine kinase receptor inhibitor-targeted combined chemotherapy for metastatic bladder cancer | |
| CN110191897A (en) | For preventing to be exposed to the treatment of the transfer of the subject of the treatment of cancer of induction p38 activation | |
| US20160058777A1 (en) | Identification and treatment of cancer subsets | |
| Findakly et al. | Molecular profiling of benign metastasizing leiomyoma of the uterus revealing unique novel therapeutic targets | |
| US20160040168A1 (en) | Composition for Treatment or Metastasis Suppression of Cancers Which Includes P34 Expression Inhibitor or Activity Inhibitor as Active Ingredient | |
| EP4285938A1 (en) | Pharmaceutical composition for treating or preventing malignant breast cancer | |
| KR102585038B1 (en) | Pharmaceutical composition for the treatment of breast cancer containing leptin receptor antagonist peptide as an active ingredient | |
| CN114908158B (en) | Use of CDK1 in diagnosis and treatment of advanced gastrointestinal stromal tumors | |
| KR20240051383A (en) | A pharmaceutical composition for preventing or treating anti-angiogenesis and/or cancer comprising ramucirumab and a FGFR2 inhibitor | |
| KR20240051379A (en) | A pharmaceutical composition for preventing or treating anti-angiogenesis and/or cancer comprising ramucirumab and a HER2 inhibitor | |
| EP1731160B1 (en) | Cancer metastasis inhibitory composition | |
| KR20240051380A (en) | A pharmaceutical composition for preventing or treating anti-angiogenesis and/or cancer comprising ramucirumab and a MET inhibitor | |
| Ma et al. | Transcriptomics and experimental validation-based approach to understand the effect and mechanism of Huangqin tang interfeience with colitis associated colorectal cancer | |
| KR20230150120A (en) | Anticancer drug and screening method by inhibiting of adipogenesis of pre-adipocytes by Gremlin-2 protein treatment or GREM2 overexpression | |
| KR20190001365A (en) | A pharmaceutical composition for inhibiting a growth of cancer stem cells comprising pyridine-based compound | |
| KR101987970B1 (en) | Pharmaceutical composition for preventing or treating cancer comprising inhibitor for expressing or activating of Asparaginyl tRNA synthetase |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| E90F | Notification of reason for final refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant |