CN113712949B - 正辛酸在制备预防和/或治疗肿瘤产品中的应用 - Google Patents
正辛酸在制备预防和/或治疗肿瘤产品中的应用 Download PDFInfo
- Publication number
- CN113712949B CN113712949B CN202111080558.1A CN202111080558A CN113712949B CN 113712949 B CN113712949 B CN 113712949B CN 202111080558 A CN202111080558 A CN 202111080558A CN 113712949 B CN113712949 B CN 113712949B
- Authority
- CN
- China
- Prior art keywords
- octanoic acid
- cells
- tumor
- cell
- lung adenocarcinoma
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 title claims abstract description 94
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 23
- 238000011282 treatment Methods 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 230000002265 prevention Effects 0.000 title abstract description 4
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims abstract description 15
- 201000005249 lung adenocarcinoma Diseases 0.000 claims abstract description 15
- 230000000259 anti-tumor effect Effects 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 9
- 230000012010 growth Effects 0.000 abstract description 8
- 206010027476 Metastases Diseases 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 238000011161 development Methods 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- 230000009401 metastasis Effects 0.000 abstract description 6
- 238000011160 research Methods 0.000 abstract description 6
- 230000002757 inflammatory effect Effects 0.000 abstract description 5
- 230000009545 invasion Effects 0.000 abstract description 5
- 210000000621 bronchi Anatomy 0.000 abstract description 4
- 208000024891 symptom Diseases 0.000 abstract description 3
- 238000000338 in vitro Methods 0.000 abstract description 2
- 230000002093 peripheral effect Effects 0.000 abstract description 2
- 208000019693 Lung disease Diseases 0.000 abstract 1
- 230000001093 anti-cancer Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 55
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical group NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 25
- 239000003814 drug Substances 0.000 description 15
- 229940079593 drug Drugs 0.000 description 13
- 239000001963 growth medium Substances 0.000 description 12
- 229960003966 nicotinamide Drugs 0.000 description 12
- 235000005152 nicotinamide Nutrition 0.000 description 12
- 239000011570 nicotinamide Substances 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 11
- 239000008194 pharmaceutical composition Substances 0.000 description 11
- 210000004881 tumor cell Anatomy 0.000 description 11
- 239000006228 supernatant Substances 0.000 description 9
- 206010061218 Inflammation Diseases 0.000 description 8
- 238000012258 culturing Methods 0.000 description 8
- 230000004054 inflammatory process Effects 0.000 description 8
- 208000020816 lung neoplasm Diseases 0.000 description 8
- 230000005012 migration Effects 0.000 description 8
- 238000013508 migration Methods 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 201000005202 lung cancer Diseases 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 5
- 125000005473 octanoic acid group Chemical group 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 235000002639 sodium chloride Nutrition 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 210000004969 inflammatory cell Anatomy 0.000 description 4
- 230000028709 inflammatory response Effects 0.000 description 4
- 108010082117 matrigel Proteins 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 239000004017 serum-free culture medium Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102100026888 Mitogen-activated protein kinase kinase kinase 7 Human genes 0.000 description 3
- 108010057466 NF-kappa B Proteins 0.000 description 3
- 102000003945 NF-kappa B Human genes 0.000 description 3
- 239000006180 TBST buffer Substances 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 108091008743 testicular receptors 4 Proteins 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 206010005003 Bladder cancer Diseases 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000007664 blowing Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000006748 scratching Methods 0.000 description 2
- 230000002393 scratching effect Effects 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- -1 small molecule compound Chemical class 0.000 description 2
- 229940126586 small molecule drug Drugs 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000009458 Carcinoma in Situ Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 1
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010062129 Tongue neoplasm Diseases 0.000 description 1
- 102000005747 Transcription Factor RelA Human genes 0.000 description 1
- 108010031154 Transcription Factor RelA Proteins 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 208000023915 Ureteral Neoplasms Diseases 0.000 description 1
- 206010046392 Ureteric cancer Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 238000012362 drug development process Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 210000002570 interstitial cell Anatomy 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 150000004667 medium chain fatty acids Chemical class 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000013334 tissue model Methods 0.000 description 1
- 201000006134 tongue cancer Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 208000010576 undifferentiated carcinoma Diseases 0.000 description 1
- 201000011294 ureter cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
-
- 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
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及正辛酸在制备预防和/或治疗肿瘤产品中的应用。肺腺癌是一种起源于支气管的周围型肺病,早期没有明显的临床症状,发现时通常为晚期。本发明目的在于进一步筛选具有抗肿瘤活性的小分子实体化合物,经研究确认,正辛酸具有良好的抗肺腺癌活性,体外研究中可以有效抑制肺腺癌的生长、转移和侵袭,并且能够通过抑制炎症因子的表达辅助改善抗癌效果,有望成为一种具有良好开发前景的小分子化合物。
Description
技术领域
本发明属于抗肿瘤活性成分技术领域,具体涉及正辛酸作为一种肿瘤抑制活性成分在制备预防和/或治疗肿瘤产品中的应用。
背景技术
公开该背景技术部分的信息仅仅旨在增加对本发明的总体背景的理解,而不必然被视为承认或以任何形式暗示该信息构成已经成为本领域一般技术人员所公知的现有技术。
肿瘤具有增殖激活、逃避凋亡、炎症反应、侵袭转移等十大特征。炎症反应在肿瘤复杂病理机制中发挥主导作用,炎症细胞会造成DNA损伤,使抑癌基因发生突变,导致肿瘤的发生;炎症细胞分泌的生长因子可与肿瘤细胞上的受体结合,促进肿瘤细胞生存和增殖,同时还能够招募其他炎症细胞至肿瘤微环境中,促使细胞增殖并诱导血管生成,从而促进肿瘤的生长;炎症反应还会加速肿瘤细胞侵入血液,形成转移灶,与炎症细胞及间质细胞相互作用,促进肿瘤细胞在转移位的生长。研究表明,抑制肺部炎症反应能抑制肺腺癌细胞增殖,减少肺腺癌的数量和体积;持续的肺部炎症导致休眠肿瘤细胞周围区域形成网状结构,酶位点暴露,诱导休眠的癌细胞重新苏醒并开始增殖;巨噬细胞增强癌细胞炎症反应,在肺内积聚是引起肺癌的主要原因;晚期非小细胞肺癌患者全身炎症水平升高与卡铂化疗后生存期明显缩短有关。由以上可知,肺癌发生发展与炎症反应密切相关,调控炎症反应是干预肺癌的重要手段。
肺腺癌(lung adenocarcinoma)是肺癌的一种,属于非小细胞癌。不同于鳞状细胞肺癌,肺腺癌较容易发生于女性及不抽烟者。起源于支气管粘膜上皮,少数起源于大支气管的粘液腺。发病率比鳞癌和未分化癌低,发病年龄较小,女性相对多见。多数腺癌起源于较小的支气管,为周围型肺癌。早期一般没有明显的临床症状,往往在胸部X线检查时被发现。表现为圆形或椭圆形肿块,一般生长较慢,早期一般没有明显的临床症状,往往在胸部X线检查时被发现。表现为圆形或椭圆形肿块,一般生长较慢,但有时早期即发生血行转移。淋巴转移则发生较晚。肺腺癌会导致支气管阻塞,原本正常肺泡囊腔消失,影响氧气与二氧化碳的交换,病人会因此感到胸闷、气短;如果肺癌得不到及时的控制,急速恶化下去,对患者的生命产生极大的威胁。
针对肺腺癌的化药开发中,小分子药物结构具有良好的空间分散性,其化学性质决定了其良好的成药性能和药物代谢动力学性质。这些特点就使得小分子药物在药物研发过程及其它药物领域中表现出巨大优势,小分子药物研发越来越受到市场的青睐。
正辛酸,为无色透明油状液体,有汗臭,微溶于热水,溶于乙醇、苯、乙醚。用于制染料、药物、香料、增塑剂、润滑剂、防腐剂、杀菌剂等。脂肪酸能够通过抑制NF-κB通路,进而抑制炎症反应,另外还可以通过抑制转化生长因子激活激酶-1(transforming growthfactor activated kinase-1,TAK1)的活化,阻止下游信号分子激活NF-κB进而抑制炎症反应,正辛酸作为中链脂肪酸,对炎症的相关作用及对肿瘤细胞的迁移作用尚未研究。
发明内容
基于上述技术背景,本发明目的在于进一步扩展抗肿瘤活性成分,提供具有开发前景的实体小分子化合物。
为了实现上述技术目的,本发明提供以下技术方案:
本发明第一方面,提供正辛酸在制备预防和/或治疗肿瘤产品中的应用。
应当说明的是,所述正辛酸除包括以下式Ⅰ所示结构的化合物实体,还包括正辛酸药学上可接受的盐、酯、溶剂化物、代谢产物或前药;所述式Ⅰ如下:
所述药学上可接受的盐,根据本领域通常的理解,通常表示正辛酸的碱金属盐,如钾盐、钠盐等。
优选的,所述预防和/或治疗肿瘤的产品为包括但不限于药物、保健品、特殊医用食品、模型药物中的一种。
优选的,所述肿瘤为包括但不限于皮肤癌,头颈癌,肺癌,食道癌,宫颈癌,子宫癌,膀胱癌,胰腺癌,乳腺癌,肾癌,输尿管癌,膀胱癌,肠道癌症,黑色素瘤,舌癌中的一种;进一步的方案中,所述肿瘤为腺癌;本发明证实的一种实施方式中,所述肿瘤为肺腺癌。
本发明第二方面,提供一种药物组合物,所述药物组合物中包括正辛酸。
本发明所述的“药物组合物”,或称“组合物”,其可用于在受试者特别是哺乳动物中实现治疗或预防本发明所述疾病。所述药物组合物优选的方案中,所述正辛酸作为活性成分,进一步的,为一种抗肿瘤活性成分。所述药物组合物中,正辛酸作为抗肿瘤活性成分,其应当是增效有效剂量的,所述药物剂量属于本领域技术可通过常规技术手段进行确定的技术内容。
本发明化合物的药物组合物,可以通过以下任意方式施与:口服、喷雾吸入、直肠给药、鼻腔给药、阴道给药、局部给药、非肠道给药如皮下、静脉、肌内、腹膜内、鞘内、心室内、胸骨内或颅内注射或输入,或借助一种外植的储器用药,其中优选口服、肌注、腹膜内或静脉内用药方式。
具体的,所述药物组合物的剂型可以是液体剂型、固体剂型;液体剂型包括但不限于真溶液类、胶体类、微粒剂型、乳剂剂型、混悬剂型;其他剂型例如片剂、胶囊、滴丸、气雾剂、丸剂、粉剂、溶液剂、混悬剂、乳剂、颗粒剂、栓剂、冻干粉针剂、包合物、填埋剂、贴剂、擦剂等。
本发明的药物组合物中还可以含有常用的载体,这里所述可药用载体包括但不局限于:离子交换剂,氧化铝,硬脂酸铝,卵磷脂,血清蛋白如人血清蛋白,缓冲物质如磷酸盐,甘油,山梨酯,山梨酸钾,饱和植物脂肪酸的部分甘油酯混合物,水,盐或电解质,如硫酸鱼精蛋白,磷酸氢二钠,磷酸氢钾,氯化钠,锌盐,胶态氧化硅,三硅酸镁,聚乙烯吡咯烷酮,纤维素物质,聚乙二醇,羧甲基纤维素钠,聚丙烯酸酯,蜂蜡,羊毛酯等。载体在药物组合物中的含量可以是1 重量%-98重量%,通常大约占到80重量%。为方便起见,局部麻醉剂,防腐剂,缓冲剂等可直接溶于载体中。
本发明第三方面,提供一种抗肿瘤或抗炎药物,所述抗肿瘤药物中包括正辛酸,或第二方面所述药物组合物。
本发明以A549肿瘤细胞作为模型,证实了正辛酸能够直接抑制A549细胞的生长,抑制肿瘤细胞迁移、侵袭,从而实现压制肿瘤组织生长、转移的作用,并从机制通路的层面为上述抗肿瘤效果提供了相应的依据,启示了所述抗肿瘤药物可作为一种原位癌治疗药物或抑制肿瘤转移的药物。
另外,本发明研究还证实了,正辛酸能够显著降低肿瘤细胞中炎性因子的表达,这一方面启示了正辛酸可能通过改善炎症发展程度实现抗肿瘤作用,另一方面,还提供了正辛酸作为一种抗炎活性成分在抗炎药物中的应用。具体的实例中,所述炎症因子为IL-6、TNF-α。
除上述药物开发的技术方案,本发明还提供上述药物在疾病治疗及作为研究试剂中的使用方式。在作为模型药物的应用方式中,本发明第四方面,提供一种抑制炎性因子或肿瘤细胞增殖、迁移、侵袭的方法,所述方法包括有需要的个体施用正辛酸、第二方面所述药物组合物或第三方面所述药物。
应当明确的是,在上述第四方面所表示的技术方案中,所述“有需要的个体”表示本领域所使用的研究模型,包括但不限于表达载体、细胞模型、组织模型或动物模型等,其中,所述动物模型优选哺乳动物模型。
本发明第五方面,提供一种肿瘤治疗方法,所述治疗方法包括有需要的个体施予正辛酸、第二方面所述药物组合物获第三方面所述药物。
所述“施予”表示采用可确定剂量的方式给药,包括但不限于服用、注射或通过手术方式如介入治疗等进行给药。
附图说明
构成本发明的一部分的说明书附图用来提供对本发明的进一步理解,本发明的示意性实施例及其说明用于解释本发明,并不构成对本发明的不当限定。
图1为实施例1中所述正辛酸对A549细胞的抑制作用;
注:“**”与烟酰胺组相比,正辛酸组具有极显著性差异,P<0.01;
图2为实施例1中所述正辛酸对A549迁移的抑制作用;
图3为实施例1中所述正辛酸对A549侵袭的抑制作用;
图4为实施例1中所述细胞上清中IL-6因子的含量测定;
注:“**”与对照组相比,正辛酸组IL-6含量具有极显著性差异,P<0.01;
图5为实施例1中所述细胞上清中TNF-α因子的含量测定;
注:“**”与对照组相比,正辛酸组TNF-α含量具有极显著性差异,P<0.01;“*”与对照组相比,正辛酸组TNF-α含量具有显著性差异,P<0.05.
图6为实施例1中所述正辛酸对A549细胞蛋白的影响;
图7为实施例1中所述正辛酸对A549细胞IKK、TAK1、NF-κB p65和I κB表达的影响;
注:“**”与对照组相比,正辛酸组TNF-α含量具有极显著性差异,P<0.01;“*”与对照组相比,正辛酸组TNF-α含量具有显著性差异,P<0.05.
具体实施方式
应该指出,以下详细说明都是例示性的,旨在对本发明提供进一步的说明。除非另有指明,本文使用的所有技术和科学术语具有与本发明所属技术领域的普通技术人员通常理解的相同含义。
需要注意的是,这里所使用的术语仅是为了描述具体实施方式,而非意图限制根据本发明的示例性实施方式。如在这里所使用的,除非上下文另外明确指出,否则单数形式也意图包括复数形式,此外,还应当理解的是,当在本说明书中使用术语“包含”和/或“包括”时,其指明存在特征、步骤、操作、器件、组件和/或它们的组合。
为了解决如上的技术问题,本发明提供了正辛酸在制备预防和/或治疗肿瘤产品中的应用。
为了使得本领域技术人员能够更加清楚地了解本发明的技术方案,以下将结合具体的实施例详细说明本发明的技术方案。
实施例1
郭健莲等人研究中,公开了烟酰胺具有体外抑制肺腺癌细胞GLC-82的增殖、迁移活性。本发明选用烟酰胺作为对照药物,对正辛酸的抗肺腺癌活性进行研究。
一、材料与方法
1.材料
药材:烟酰胺、正辛酸
细胞:人肺腺癌细胞A549
2.方法
2.1细胞培养
从超低温冰箱中取出A549细胞种子,于37℃水浴锅中快速融化。将融化好的冻存液在生物安全柜中轻轻吹打转移至2mL EP管中,1000r/min离心3 min,弃去上清液,然后向EP管中加入DMEM高糖培养基(含10%胎牛血清) 2mL,将细胞吹散转移至培养瓶中,补足培养基至5mL,放在37℃、5%CO2培养箱中培养,用于接下来的实验。
2.2药物对细胞的抑制作用
将生长对数期的A549细胞用胰蛋白酶消化吹打均匀,按照1×105的密度接种于96孔板,将板放置于37℃培养箱中进行培养孵育,待细胞密度长至90%后,吸去培养基,将烟酰胺、正辛酸分别从1mg/mL分别二倍稀释九个浓度,加至细胞中,设置细胞对照组,每个浓度分别重复四个复孔,继续培养24h,24 h后取出96孔板,弃去培养基,每孔加入稀释好的CCK8 100μL,将细胞培养板置于37℃黑暗环境培养2h后,用酶标仪测定450nm处每孔的吸光度OD 值,然后参照下面公式计算细胞存活率、抑制率。
细胞存活率=[(给药组平均OD值-校准平均OD值)/(细胞对照组平均 OD值-校准平均OD值)]×100%
细胞抑制率=1-细胞存活率
2.3划痕
将生长对数期的A549细胞用胰蛋白酶消化吹打均匀,按照1×106的密度接种于6孔板,将板放置于37℃培养箱中进行培养孵育,待细胞密度长至95%后,吸去培养基,用200μL黄色枪头垂直于6孔板底部划痕,划痕后用PBS洗细胞3次,去处划下的细胞,加入用无血清培养基稀释的烟酰胺、正辛酸,设置细胞对照组,每个浓度分别重复3个复孔,继续培养24h,24h后取出6孔板,弃去培养基,荧光倒置显微镜下观察拍照。
2.4 Transwell
将生长对数期的A549细胞用胰蛋白酶消化吹打均匀,按照1×106的密度接种于6孔板,将板放置于37℃培养箱中进行培养孵育,待细胞密度长至90%后,吸去培养基,加入用无血清培养基稀释的烟酰胺、正辛酸,设置细胞对照组,每个浓度分别重复3个复孔,继续培养24h。24h后,将基质胶与冷培养基1: 9的比例稀释,将Transwell小室放入24孔板内,每孔滴入25μL稀释好的基质胶,滴入后迅速震荡,使基质胶均匀的铺在小室底部,37℃孵育30min。将6 孔板中的细胞消化、计数后,每个小室中加入500μL无血清培养基,在下室加入600μL完全培养基(10%FBS),将24孔板放入37℃培养箱培养,24h后将24孔板取出,小室放入500μL的4%组织固定液中固定20min,吸出组织固定液后,加入500μL的0.1%结晶紫染色30min,擦去基质胶,洗去多余结晶紫及背景色,将上室、24孔板倒置晾干,拍照。
2.5 ELISA法
将生长对数期的A549细胞用胰蛋白酶消化吹打均匀,按照1×105的密度接种于96孔板,将板放置于37℃培养箱中进行培养孵育,待细胞密度长至90%后,吸去培养基,将烟酰胺、正辛酸分别从1mg/mL分别二倍稀释,加至细胞中,设置细胞对照组,每个浓度分别重复四个复孔,继续培养24h,24h后取出 96孔板,取上清,根据ELISA试剂盒说明书测定上清中IL-6和TNF-α因子的含量。
2.6 Western Blot
将A549细胞按照1×106的密度接种于6孔板培养,待细胞密度长至90%后,吸去培养基,加入用无血清培养基稀释的烟酰胺、正辛酸,设置细胞对照组,每个浓度分别重复3个复孔,继续培养24h。24h后,用预冷的PBS洗两遍,消化离心,收集细胞,加入预先配好的IP裂解液,冰上裂解30min,离心取上清得到蛋白样品。采用BCA法进行蛋白定量,绘制标准曲线,根据曲线计算待测样品的蛋白浓度,用5×上样缓冲液和细胞裂解液稀释,将待测样品蛋白浓度调整为25μg/μL。然后100℃加热5min,冷却后混匀,变性后的蛋白样品于-80℃保存。取各组样品蛋白10μg上样,经SDS-PAGE电泳分离后,转移至PVDF 膜上,封闭液封闭1h,TBST洗涤3次,一抗TAK1、NF-κB p65、IKK、IκB 和GADPH 4℃孵育过夜后,TBST洗涤3次,HRP标记二抗室温摇床1h, TBST洗涤后ECL发光,显影,定影,通过Image J软件分析目的蛋白相对灰度值的差异。
二、结果
1.药物对A549细胞的抑制作用
烟酰胺和正辛酸不同浓度对A549细胞均有一定的抑制作用。从表1和图1 可以看出,正辛酸的抑制作用明显大于烟酰胺,正辛酸的IC50为20.66,烟酰胺的IC50为190.74。
表1.烟酰胺和正辛酸对A549细胞的抑制作用
2.划痕实验
从图中可以看出,与阴性对照组相比,给药24h后,正辛酸能抑制A549细胞的迁移。
3.Transwell实验
烟酰胺和正辛酸均能抑制A549细胞的迁移。从图中可以看出,与阴性对照组相比,给药24h后,正辛酸组细胞数量明显减少。
4.ELISA
从图表中可以看出,正辛酸组细胞上清液中IL-6(表2)和TNF-α(表3) 的含量均显著低于阴性对照组,表明正辛酸能够通过降低炎症反应来实现抗肿瘤的效果。
表2.细胞上清中IL-6因子的含量测定
表3.细胞上清中TNF-α因子的含量测定
5.Western Blot
Western Blot分析结果如图6所示,与阴性对照组相比,正辛酸组可显著降低细胞中IKK、TAK1、NF-κB p65和IκB的表达,表明正辛酸能通过抑制 TAK1/NF-κB通路从而抑制肿瘤细胞的侵袭迁移。
以上所述仅为本发明的优选实施例而已,并不用于限制本发明,对于本领域的技术人员来说,本发明可以有各种更改和变化。凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (1)
1.正辛酸在制备治疗肿瘤产品中的应用,其中,所述肿瘤为肺腺癌。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111080558.1A CN113712949B (zh) | 2021-09-15 | 2021-09-15 | 正辛酸在制备预防和/或治疗肿瘤产品中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111080558.1A CN113712949B (zh) | 2021-09-15 | 2021-09-15 | 正辛酸在制备预防和/或治疗肿瘤产品中的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113712949A CN113712949A (zh) | 2021-11-30 |
CN113712949B true CN113712949B (zh) | 2023-07-25 |
Family
ID=78683860
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111080558.1A Active CN113712949B (zh) | 2021-09-15 | 2021-09-15 | 正辛酸在制备预防和/或治疗肿瘤产品中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113712949B (zh) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016210405A2 (en) * | 2015-06-26 | 2016-12-29 | University Of Florida Research Foundation, Incorporated | Method of treating inflammation using natural compounds and/or diet |
-
2021
- 2021-09-15 CN CN202111080558.1A patent/CN113712949B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016210405A2 (en) * | 2015-06-26 | 2016-12-29 | University Of Florida Research Foundation, Incorporated | Method of treating inflammation using natural compounds and/or diet |
Non-Patent Citations (4)
Title |
---|
Caprylate-Conjugated Cisplatin for the Development of Novel Liposomal;Imran Vhora等;《AAPS PharmSciTech》;20140404;1-13 * |
余元勋等.生酮饮食.《中国分子神经病学》.2015, * |
生酮饮食对人肺癌裸鼠皮下移植瘤的作用和相关机制研究;田艳等;《广东医学》;20180319(第05期);670-674 * |
田艳等.生酮饮食对人肺癌裸鼠皮下移植瘤的作用和相关机制研究.《广东医学》.2018,(第05期), * |
Also Published As
Publication number | Publication date |
---|---|
CN113712949A (zh) | 2021-11-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10245240B2 (en) | Treatment of prostate carcinoma | |
Buchheit et al. | The regulation of cancer cell death and metabolism by extracellular matrix attachment | |
CN104856996B (zh) | 吡咯喹啉醌、其衍生物和/或盐新的药用用途以及药用组合物 | |
US9486467B2 (en) | Method of treating colorectal cancer that expresses a mutated APC gene by administering erythromycin or tylosin | |
WO2023115766A1 (zh) | 槲皮素的氧甲基修饰物在制备抑制肿瘤细胞增殖的药物中的应用 | |
US10959977B2 (en) | Application of phosphodiesterase 4 inhibitor ZL-n-91 in preparation of medications for lung cancer proliferation and metastasis | |
CN103860529A (zh) | 金色灰绿曲霉素类化合物的新用途 | |
US20210353580A1 (en) | Application of chlorogenic acid and compositions thereof in preparation of drugs for treating squamous cell carcinoma | |
CN113712949B (zh) | 正辛酸在制备预防和/或治疗肿瘤产品中的应用 | |
EP2687211A1 (en) | Use of phenethyl caffeate derivatives in the preparation of a medicament against tumor angiogenesis | |
CN102441168A (zh) | 含芹菜素及芹菜素类衍生物和Bcl-2抑制剂的药物组合物及其在制备治疗癌症的药物中的应用 | |
WO2020087938A1 (zh) | 脾酪氨酸激酶作为肝内胆管细胞癌治疗靶点的应用 | |
CN113181166A (zh) | 莪术烯醇在制备治疗抗肺癌药物中的应用、抗肺癌药物 | |
EP4041922A1 (en) | Methods for treating wild type isocitrate dehydrogenase 1 cancers | |
CN111956632B (zh) | 一种抗肿瘤的组合物及其应用 | |
KR102249814B1 (ko) | 칼키톡신 티오아마이드 알코올 또는 이의 염을 유효성분으로 함유하는 암전이 억제용 조성물 | |
Yang et al. | Effect of emodin combined with cisplatin on the invasion and migration of HepG2 hepatoma cells | |
CN116549478B (zh) | 一种药物组合物及其制备方法和用途 | |
EP4342463A1 (en) | Stilbene compounds for use in the treatment of tumour and eye diseases | |
CN113663075B (zh) | Pcsk9抑制剂在制备治疗或辅助治疗肿瘤的药物中的应用 | |
CN105878253A (zh) | 科罗索酸的医药用途 | |
WO2023061464A1 (zh) | 2,3-二甲氧基-5-甲基-1,4-苯醌烷基醇衍生物及其应用 | |
CN116687904A (zh) | 截短侧耳素抗生素在制备抗肿瘤及逆转分子靶向治疗耐药的药物中的应用 | |
CN114870021A (zh) | 包含ezh2抑制剂和多不饱和脂肪酸抑制剂的抗肿瘤药物组合物及其用途 | |
CN118403048A (zh) | 莫西菌素在治疗乳头型颅咽管瘤中的应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |