CN115607676B - 羧基苍术苷在制备抗肿瘤耐药性的药物中的应用 - Google Patents
羧基苍术苷在制备抗肿瘤耐药性的药物中的应用 Download PDFInfo
- Publication number
- CN115607676B CN115607676B CN202211277740.0A CN202211277740A CN115607676B CN 115607676 B CN115607676 B CN 115607676B CN 202211277740 A CN202211277740 A CN 202211277740A CN 115607676 B CN115607676 B CN 115607676B
- Authority
- CN
- China
- Prior art keywords
- osteosarcoma
- drug resistance
- carboxyatractyloside
- application
- tumor
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 29
- 206010059866 Drug resistance Diseases 0.000 title claims abstract description 24
- CYBVQIBJEFQVPD-GWDNDVLHSA-N carboxyatractyloside Chemical compound O1[C@@H](COO)[C@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@@H](OC(=O)CC(C)C)[C@H]1O[C@H]1CC(C(O)=O)(C(O)=O)[C@@H]2CC[C@@]3([C@@H](O)C4=C)C[C@H]4CC[C@@H]3[C@@]2(C)C1 CYBVQIBJEFQVPD-GWDNDVLHSA-N 0.000 title claims abstract description 16
- 229940079593 drug Drugs 0.000 title abstract description 17
- 239000002246 antineoplastic agent Substances 0.000 title description 6
- 229940041181 antineoplastic drug Drugs 0.000 title description 5
- 238000002360 preparation method Methods 0.000 title description 4
- 201000008968 osteosarcoma Diseases 0.000 claims abstract description 29
- 210000001700 mitochondrial membrane Anatomy 0.000 claims abstract description 11
- 239000011148 porous material Substances 0.000 claims abstract description 10
- 230000037050 permeability transition Effects 0.000 claims abstract description 7
- 230000037396 body weight Effects 0.000 claims description 2
- 239000007928 intraperitoneal injection Substances 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 20
- 210000004027 cell Anatomy 0.000 abstract description 20
- FYQXODZRNSCOTR-UHFFFAOYSA-N atractyloside Natural products O1C(CO)C(OS(O)(=O)=O)C(OS(O)(=O)=O)C(OC(=O)CC(C)C)C1OC1CC2(C)C3CCC(C(=C)C4O)CC34CCC2C(C(O)=O)C1 FYQXODZRNSCOTR-UHFFFAOYSA-N 0.000 abstract description 7
- 238000011160 research Methods 0.000 abstract description 6
- -1 carboxyl atractyloside Chemical compound 0.000 abstract description 4
- 230000008261 resistance mechanism Effects 0.000 abstract description 2
- 229960004316 cisplatin Drugs 0.000 description 19
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 19
- 241000699660 Mus musculus Species 0.000 description 9
- 238000011580 nude mouse model Methods 0.000 description 9
- 101710103970 ADP,ATP carrier protein Proteins 0.000 description 8
- 101710133192 ADP,ATP carrier protein, mitochondrial Proteins 0.000 description 8
- 108010067028 Mitochondrial Permeability Transition Pore Proteins 0.000 description 8
- 102100031414 EF-hand domain-containing protein D1 Human genes 0.000 description 7
- 101000866909 Homo sapiens EF-hand domain-containing protein D1 Proteins 0.000 description 7
- 210000000988 bone and bone Anatomy 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 229940044683 chemotherapy drug Drugs 0.000 description 5
- 230000002438 mitochondrial effect Effects 0.000 description 5
- 102100026397 ADP/ATP translocase 3 Human genes 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 101710148588 ADP,ATP carrier protein 2 Proteins 0.000 description 2
- 101710165307 ADP,ATP carrier protein 2, mitochondrial Proteins 0.000 description 2
- 101710102718 ADP/ATP translocase 2 Proteins 0.000 description 2
- 102100026396 ADP/ATP translocase 2 Human genes 0.000 description 2
- 101710102715 ADP/ATP translocase 3 Proteins 0.000 description 2
- IUCNQFHEWLYECJ-FNAJZLPOSA-L Atractyloside Chemical compound [K+].[K+].O1[C@H](CO)[C@@H](OS([O-])(=O)=O)[C@H](OS([O-])(=O)=O)[C@@H](OC(=O)CC(C)C)[C@@H]1O[C@H]1C[C@@]2(C)[C@@H]3CC[C@@H](C(=C)[C@@H]4O)C[C@]34CC[C@@H]2[C@H](C(O)=O)C1 IUCNQFHEWLYECJ-FNAJZLPOSA-L 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- 101000718417 Homo sapiens ADP/ATP translocase 2 Proteins 0.000 description 2
- 101000718437 Homo sapiens ADP/ATP translocase 3 Proteins 0.000 description 2
- 241000209094 Oryza Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 101710172711 Structural protein Proteins 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000009670 cang er zi wan Substances 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 238000013414 tumor xenograft model Methods 0.000 description 2
- JNELGWHKGNBSMD-UHFFFAOYSA-N xanthone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3OC2=C1 JNELGWHKGNBSMD-UHFFFAOYSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- TTWQJTZYBXHGKQ-UHFFFAOYSA-N 9h-xanthene-1-carboxylic acid Chemical compound O1C2=CC=CC=C2CC2=C1C=CC=C2C(=O)O TTWQJTZYBXHGKQ-UHFFFAOYSA-N 0.000 description 1
- 108040000931 ATP:ADP antiporter activity proteins Proteins 0.000 description 1
- 102000023805 ATP:ADP antiporter activity proteins Human genes 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 241000208838 Asteraceae Species 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 206010051728 Bone erosion Diseases 0.000 description 1
- 102000034573 Channels Human genes 0.000 description 1
- 101150096151 EFHD1 gene Proteins 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108020005196 Mitochondrial DNA Proteins 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 206010062575 Muscle contracture Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 238000003559 RNA-seq method Methods 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 241001506766 Xanthium Species 0.000 description 1
- 241001251949 Xanthium sibiricum Species 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 208000006111 contracture Diseases 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003777 experimental drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000030175 lameness Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 150000007965 phenolic acids Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了羧基苍术苷在制备抗肿瘤耐药性的药物中的应用，涉及药物新用途的技术领域。本发明通过对骨肉瘤耐药机制的研究，发现线粒体膜通透性转换孔可作为治疗耐药性骨肉瘤的新靶点，进一步研究发现，羧基苍术苷能够有效缓解骨肉瘤细胞系的耐药情况。本发明将羧基苍术苷应用于耐药性骨肉瘤，不仅为制备抗骨肉瘤耐药性的药物提供了一种新来源，同时发掘出了羧基苍术苷新的药用价值。
Description
技术领域
本发明涉及药物新用途的技术领域，具体涉及羧基苍术苷在制备抗肿瘤耐 药性的药物中的应用。
背景技术
骨肉瘤(osteosacoma)也叫成骨肉瘤，是较常见的发生在20岁以下的青少 年或儿童的一种恶性骨肿瘤，在小儿骨恶性肿瘤中最多见。骨肉瘤是骨恶性肿 瘤中最多见的一种，是从间质细胞系发展而来，肿瘤迅速生长是由于肿瘤经软 骨阶段直接或间接形成肿瘤骨样组织和骨组织。骨肉瘤好发于四肢长骨的干骺 端，其突出的临床表现为肿瘤细胞的快速增殖导致的骨质破坏，骨皮质侵蚀引 起剧烈的疼痛，伴随着疼痛引起的跛行等。目前治疗方式包括化疗，外科手术，靶向药物治疗等，其中化疗是治疗骨肉瘤最主要和最关键的治疗措施。目前以 顺铂、多柔比星和甲氨蝶呤为基础的化疗药物治疗骨肉瘤。骨肉瘤对化疗药物 耐药是骨肉瘤患者存活率在过去的30年里没有再次提高的重要原因之一。骨肉 瘤主要通过原发性和继发性耐药2种方式发挥化疗耐药作用。因此，探索骨肉 瘤抗化疗的分子机制并找到相应的克服方式，对提高OS患者的生存率具有重要 的意义。
苍耳子为菊科植物苍耳的干燥成熟果实提取物，味辛、苦、温，有毒，归 肺经。主要含有挥发油、脂肪油、酚酸、苍耳子噻嗪双酮等杂环类化合物、蒽 醌、黄酮、生物碱及其他类成分，苍耳子有散风寒、通鼻窍、祛风湿的功效， 主要用于风寒头痛，鼻渊流涕，鼻渊，风疹瘙痒，湿痹拘挛等症的治疗，为历 代治疗鼻渊头痛的要药。苍术苷(ATR，atractyloside)和羧基苍术苷(CAT， carboxyatractyloside)及其衍生物为苍耳子中的重要成分。
目前，苍耳子被用于呼吸道疾病治疗药物和心血管治疗药物的制备中，但 目前未见其具有抗肿瘤耐药性功效的报道。
发明内容
本发明的目的在于克服现有技术的不足，提供羧基苍术苷在制备抗肿瘤耐 药性的药物中的应用。
为实现上述目的，本发明采取的技术方案为：提供以线粒体膜通透性转换 孔作为靶点在制备抗肿瘤耐药性的药物中的应用。研究表明，线粒体膜通透性 转换孔(mitochondrial permeablity transition pore，mPTP)，又称线粒体巨型通 道(magachannel)，是存在于线粒体内外膜之间的一组蛋白复合体，由多种蛋白质复合组成，是存在于线粒体内外膜之间的一种非特异性高导电性通道，可 能参与了细胞死亡过程中线粒体成分的释放，在细胞的生存、凋亡中扮演着重 要角色，它涉及肿瘤、衰老、神经变性等多个领域。本申请发明人研究发现， 在RNAsequencing数据中线粒体基因EFHD1在化疗耐药的组别中存在较高的表达，而体外诱导的143BR(耐顺铂耐药细胞株)中EFHD1也存在高表达，通 过对其中机制的深入研究，本申请发明人发现EFHD1可以通过与ANT2或ANT3 结合，进而抑制mPTP孔的开放，促进细胞存活，进而介导顺铂化疗耐药。由 此说明，线粒体膜通透性转换孔可作为治疗耐药性骨肉瘤的新靶点。
作为本发明所述应用的优选实施方式，所述肿瘤为骨肉瘤。
作为本发明所述应用的优选实施方式，所述药物能够促进线粒体膜通透性 转换孔开放。
本发明还提供ANT抑制剂在制备抗肿瘤耐药性的药物中的应用。ANT蛋白 家族是一类线粒体内膜ATP/ADP转运通道蛋白，其功能的发挥依赖于m-state (开口朝向线粒体基质)和c-state(开口朝向胞浆)的转变。研究表明，当其处 于m-state的时候，mPTP孔开放减少；而当其处于c-state的时候，mPTP孔开 放增加。本申请发明人经过实验研究发现，EFHD1促进肿瘤增殖和耐药的能力 依赖于与mPTP结构蛋白ANT2/3结合。因此，通过抑制ANT蛋白的功能，使 其稳定在c-state，从而促进mPTP孔开放，减少耐药性。
作为本发明所述应用的优选实施方式，所述肿瘤为骨肉瘤。
作为本发明所述应用的优选实施方式，所述ANT抑制剂包括ANT2抑制剂 或ANT3抑制剂。
作为本发明所述应用的优选实施方式，所述的ANT抑制剂为羧基苍术苷。
羧基苍术苷是一种有毒性的天然产物，为ADP/ATP载体蛋白抑制剂，抑制 线粒体ADP/ATP的转运。本申请发明人研究发现，ANT蛋白家族抑制剂羧基苍 术苷可以抑制ANT蛋白的功能，使其稳定在c-state，从而促进mPTP孔开放。 采用羧基苍术苷和顺铂注射骨肉瘤模型小鼠，能够有效的缓解骨肉瘤细胞系的 耐药情况。
作为本发明所述应用的优选实施方式，所述药物的用量为1mg/kg体重/天。
作为本发明所述应用的优选实施方式，所述药物的给药方式为腹腔注射。
本发明还提供一种药物组合物，所述药物组合物包括羧基苍术苷和药学上 可接受的载体。
本发明的有益效果：本发明提供羧基苍术苷在制备抗肿瘤耐药性的药物中 的应用，本发明通过对骨肉瘤耐药机制的研究，发现线粒体膜通透性转换孔可 作为治疗耐药性骨肉瘤的新靶点，进一步研究发现，羧基苍术苷能够有效缓解 骨肉瘤细胞系的耐药情况。本发明将羧基苍术苷应用于耐药性骨肉瘤，不仅为 制备抗骨肉瘤耐药性的药物提供了一种新来源，同时发掘出了羧基苍术苷新的药用价值。
附图说明
图1为各组小鼠肿瘤的大小和重量比较图。
具体实施方式
以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的 详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基 于本发明上述内容所实现的技术均属于本发明的范围。
实施例1
1、实验材料：
(1)实验动物和细胞：六周龄的裸鼠(BALB/c-nu/nu)，体重约为15g左 右，随机分为12组，每组6只；143B耐顺铂耐药细胞株(143BR)、骨肉瘤细 胞系143B。
(2)实验药物：顺铂：购于；羧基苍术苷：购于；米酵菌酸：购于。
2、实验方法：
(1)肿瘤异种移植模型构建
在骨肉瘤细胞系143B中通过慢病毒转染构建了过表达空载体细胞系(143B-V)，过表达EFHD1基因的细胞系(143B-EFHD1)；同时通过对143B 进行为期一年的顺铂诱导，构建了143B耐顺铂耐药株，命名为143BR，检测其 EFHD1分子的表达量，发现其EFHD1分子表达量升高，故而在143BR中构建 了干扰空载体细胞系(143BR-shV)和干扰EFHD1细胞系(143BR-shEFHD1)。 以1*107/只接种到裸鼠的腹股沟皮下，构建肿瘤异种移植模型。
(2)给药：将上述小鼠分为12组，分别为：
143B-V组(为接种了143B-V细胞的模型裸鼠注射顺铂)；
143B-V对照组；
143B-EFHD1组(为接种了143B-EFHD1细胞的模型裸鼠注射顺铂)；
143B-EFHD1对照组；
143B-EFHD1+CART对照组(为接种了143B-EFHD1细胞的模型裸鼠注射 羧基苍术苷)；
143B-EFHD1+CART组(为接种了143B-EFHD1细胞的模型裸鼠注射羧基 苍术苷和顺铂)；
143BR-shV对照组；
143BR-shV组(为接种了143BR-shV细胞的模型裸鼠注射顺铂)；
143B-EFHD1对照组；
143B-EFHD1组(为接种了143B-EFHD1的模型裸鼠注射米酵菌酸和顺铂)；
143BR-shEFHD1+BKA对照组；
143BR-shEFHD1+BKA组(为接种了143BR-shEFHD1的模型裸鼠注射米酵 菌酸和顺铂)。
在接种肿瘤生长至约100mm3(肿瘤的大小按照长径*短径2/2计算)时，腹 腔注射顺铂(3mg/kg/天)、羧基苍术苷(1mg/kg/天)、米酵菌酸(0.5mg/kg/ 天)。
(3)观察肿瘤的大小：接种肿瘤12天后开始测量肿瘤的大小，每三天一 次，直到31天为止。肿瘤的大小按照长径*短径2/2计算。在31天以后，处 死小鼠，取下肿瘤拍照并称重。
(4)结果如图1所示。由图1可知，EFHD1具有促进肿瘤增殖和耐药性， 而其发挥促进耐药的功能依赖于与mPTP结构蛋白ANT2/3结合。通过使用顺铂和羧基苍术苷、米酵菌酸注射小鼠，可以看出羧基苍术苷和顺铂能有效的 缓解骨肉瘤细胞系的耐药情况；而米酵菌酸和顺铂则可以使得肿瘤对顺铂的 耐药性增强。
最后应当说明的是，以上实施例仅用以说明本发明的技术方案而非对本发 明保护范围的限制，尽管参照较佳实施例对本发明作了详细说明，本领域的普 通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不 脱离本发明技术方案的实质和范围。
Claims (4)
1.羧基苍术苷作为唯一活性成分在制备抗骨肉瘤耐药性的药物中的应用。
2.根据权利要求1所述的应用，其特征在于，所述药物促进线粒体膜通透性转换孔开放。
3.根据权利要求1所述的应用，其特征在于，所述药物的用量为1 mg/kg体重/天。
4.根据权利要求1所述的应用，其特征在于，所述药物的给药方式为腹腔注射。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211277740.0A CN115607676B (zh) | 2022-10-19 | 2022-10-19 | 羧基苍术苷在制备抗肿瘤耐药性的药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211277740.0A CN115607676B (zh) | 2022-10-19 | 2022-10-19 | 羧基苍术苷在制备抗肿瘤耐药性的药物中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115607676A CN115607676A (zh) | 2023-01-17 |
| CN115607676B true CN115607676B (zh) | 2024-03-01 |
Family
ID=84863688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211277740.0A Active CN115607676B (zh) | 2022-10-19 | 2022-10-19 | 羧基苍术苷在制备抗肿瘤耐药性的药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115607676B (zh) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010003232A1 (en) * | 2008-07-07 | 2010-01-14 | Constab Pharmaceutical Inc. | Treating cancer using atractyloside |
| DE202022100610U1 (de) * | 2022-02-03 | 2022-02-23 | Jothieswari Dhamotharan | Ein System zur Verabreichung von Nanoträgern bei Osteosarkomen und zur Überwindung der Resistenz gegen Krebsmedikamente |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7622549B2 (en) * | 1997-04-18 | 2009-11-24 | Geron Corporation | Human telomerase reverse transcriptase polypeptides |
-
2022
- 2022-10-19 CN CN202211277740.0A patent/CN115607676B/zh active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010003232A1 (en) * | 2008-07-07 | 2010-01-14 | Constab Pharmaceutical Inc. | Treating cancer using atractyloside |
| DE202022100610U1 (de) * | 2022-02-03 | 2022-02-23 | Jothieswari Dhamotharan | Ein System zur Verabreichung von Nanoträgern bei Osteosarkomen und zur Überwindung der Resistenz gegen Krebsmedikamente |
Non-Patent Citations (2)
| Title |
|---|
| Conformational change of adenine nucleotide translocase-1 mediates cisplatin resistance induced by EBV-LMP1;Lin Zhao，等;《EMBO Molecular Medicine》;第13卷;摘要和正文第2-13页 * |
| Lack of Oxidative Phosphorylation and Low Mitochondrial Membrane Potential Decrease Susceptibility to Apoptosis and Do Not Modulate the Protective Effect of Bcl-xL in Osteosarcoma Cells;Runu Dey，等;《THE JOURNAL OF BIOLOGICAL CHEMISTRY》;第275卷(第10期);第7087-7094页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115607676A (zh) | 2023-01-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101801639B1 (ko) | 테트라하이드로카나비놀 및 카나비다이올을 포함하는 뇌종양 치료용 약학적 조성물 | |
| Park et al. | Dehydrocostuslactone inhibits LPS-induced inflammation by p38MAPK-dependent induction of hemeoxygenase-1 in vitro and improves survival of mice in CLP-induced sepsis in vivo | |
| KR101891505B1 (ko) | 혈구 감소를 예방 또는 치료하기 위한 약물의 제조에 있어서의 안히드로이카리틴의 용도 | |
| Chen et al. | Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil–based chemotherapy in colorectal cancer | |
| CN104398526B (zh) | 雷公藤甲素和雷公藤红素在制备抗肿瘤药物中的应用 | |
| CN109575100A (zh) | 甘氨胆酸在制备抗肿瘤药物中的应用 | |
| US9901602B2 (en) | Ejaculum of animals as medicinal material and uses thereof in medicaments for treatment of diseases such as tumors, depression, etc | |
| CN109350613B (zh) | 一种治疗癌症的姜黄素复方制剂 | |
| CN113925867A (zh) | 盐酸决奈达隆联合5-氟尿嘧啶在制备抗肿瘤药物中的应用 | |
| JP2022019937A (ja) | ヒト又は動物の慢性若しくは急性のウイルス感染症及び／又は敗血症の予防若しくは治療のための組成物 | |
| CN115607676B (zh) | 羧基苍术苷在制备抗肿瘤耐药性的药物中的应用 | |
| CN116726021A (zh) | 一种drp1抑制剂和铁死亡诱导剂联合用药物及其抗肿瘤的用途 | |
| CN102319260A (zh) | 顺铂联合伊曲康唑异构体在制备治疗肺癌药物中的应用 | |
| CN107308121A (zh) | 肝脏再生的治疗剂 | |
| CN106038566B (zh) | 一种用于胃癌治疗的药物组合物及其应用 | |
| CN110559287A (zh) | 一种用于治疗癌症的药物组合物及其应用 | |
| CN107281177B (zh) | 促进造血干细胞归巢和植入的方法 | |
| CN105233285B (zh) | Epac直接或间接激动剂与溶瘤病毒的联合应用 | |
| CN111632146B (zh) | Oat抑制剂和溶瘤病毒在制备抗肿瘤药物中的应用 | |
| KR102328367B1 (ko) | 아젤록심 d를 유효성분으로 함유하는 방사선 민감성 증진용 조성물 | |
| CN112773793B (zh) | 表观遗传因子抑制剂40569z在制备抗肝癌药物增敏剂中的应用 | |
| KR101473903B1 (ko) | 방사선 조사에 의한 알로에 에모딘의 항암 활성 증진 방법 및 방사선이 조사된 알로에 에모딘을 유효성분으로 포함하는 암 예방 또는 치료용 조성물 | |
| CN102526033B (zh) | 由表没食子儿茶素没食子酸酯与丝裂霉素c制成的抑制肿瘤细胞增殖的组合物 | |
| CN116251095A (zh) | 银杏内酯b在制备预防肿瘤转移的药物中的应用 | |
| NL1013004C1 (nl) | Kruidensamenstelling geschikt voor de bereiding van een farmaceutisch preparaat voor het behandelen van kanker, een extract en een farmaceutisch preparaat. |
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 |