

浏览全部资源
扫码关注微信
1.北京中医药大学 中药学院 中药现代研究中心,北京 100029
2.滨州医学院 药学院,山东 烟台 264003
Received:22 June 2021,
Published Online:02 September 2021,
Published:05 January 2022
移动端阅览
黄惠铭,杨爱琳,田颖颖等.肿瘤耐药性产生机制及中药逆转作用的研究进展[J].中国实验方剂学杂志,2022,28(01):92-99.
HUANG Hui-ming,YANG Ai-lin,TIAN Ying-ying,et al.Mechanism of Cancer Drug Resistance and Reversal Effect of Chinese Medicine: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(01):92-99.
黄惠铭,杨爱琳,田颖颖等.肿瘤耐药性产生机制及中药逆转作用的研究进展[J].中国实验方剂学杂志,2022,28(01):92-99. DOI: 10.13422/j.cnki.syfjx.20212122.
HUANG Hui-ming,YANG Ai-lin,TIAN Ying-ying,et al.Mechanism of Cancer Drug Resistance and Reversal Effect of Chinese Medicine: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(01):92-99. DOI: 10.13422/j.cnki.syfjx.20212122.
恶性肿瘤严重危害人类生命和健康,我国癌症发病率和死亡率逐年上升,攻克肿瘤一直以来都是人类生存的一大难题。化学药物和分子靶向治疗是抗肿瘤临床通用方案,也是首选方案之一,此类药物靶标明确、疗效好,但不良反应大,且肿瘤细胞常常产生耐药性阻碍药效的发挥,从而使肿瘤治疗变得困难,故研究耐药性的产生机制及如何逆转耐药性具有重要的意义。聚焦中药,多年研究发现,其拥有成分复杂、靶点繁多、方组内药味相辅相成、毒性小等居多特点,大量实验研究证明,中药有效成分或其提取部位能够明显抑制肿瘤细胞增殖、迁移、侵袭,诱导其凋亡、自噬、分化、衰老等。临床上已将中药运用于肿瘤的防护、辅助治疗、后期巩固等,中药研究将为逆转肿瘤细胞耐药性及抑制肿瘤细胞开启不一样的新篇章。已有研究表明,中药与化疗药物联用可逆转肿瘤细胞耐药性,增加化疗药物疗效,现已成为肿瘤治疗的主流趋势。此文就肿瘤细胞由保护性自噬、基因突变、酶系的过高表达、信号通路异常、核糖核酸和相关蛋白表达异常等所产生的耐药性机制,以及从中药中分离出的单体成分、单药或其提取部位及经典抗癌名方逆转肿瘤细胞耐药性的机制进行综述,为进一步研究中药抗肿瘤作用奠定基础。
Malignant tumor is a serious threat to human life and health. The prevalence and mortality of malignancies in China are increasing year by year. Conquering cancer has become a difficult problem for human beings. Chemical drug therapy combined with molecular targeted therapy is a general and preferred anti-tumor clinical scheme, but the side effects and the drug resistance of cancer cells often hinder the efficacy. Therefore, it is of great significance to study the mechanism of drug resistance and the methods to reverse drug resistance. Chinese medicine has the characteristics of complex components, multiple targets, low toxicity, etc. A large number of experimental studies have demonstrated that the effective components or extracts of Chinese medicine can inhibit the proliferation, migration, and invasion of cancer cells, and induce apoptosis, autophagy, differentiation, and senescence. In clinical practice, Chinese medicine has been applied to the protection against ttumor, adjuvant treatment, and later consolidation. The research on Chinese medicine is expected to promote drug resistance reversal and cancer therapy. Studies have shown that the combination of Chinese medicine and chemotherapy can reverse drug resistance and increase efficacy, which has become the mainstream trend of cancer treatment. This study reviewed the mechanisms of the drug resistance of cancer cells induced by self-protective autophagy, gene mutation, high expression of enzymes, abnormal signaling pathways, and abnormal expression of RNA and protein, and summarized how compounds isolated from Chinese medicine, single drug and its extract, and classic anti-cancer prescription reversed the drug resistance to lay a solid foundation for the further investigation of the anti-tumor effect of Chinese medicine.
张依然 , 金文敏 . 肿瘤内科治疗的现状和发展 [J]. 中华肿瘤防治杂志 , 2018 , 25 ( S1 ): 311 - 312 .
王越 , 沈灿 , 胡正军 , 等 . 中医药逆转胰腺癌耐药性的研究进展 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 11 ): 220 - 227 .
YANG Y , BAI L L , LIAO W T , et al . The role of non-apoptotic cell death in the treatment and drug-resistance of digestive tumors [J]. Exp Cell Res , 2021 , 405 ( 2 ): 112678 .
颜彬 , 周钱梅 . 肿瘤相关巨噬细胞参与化疗耐药及中医药干预研究进展 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 17 ): 193 - 202 .
阿地力江·萨吾提 , 木塔力甫·艾买提 , 周文婷 , 等 . 山柰酚逆转MCF-7/阿霉素细胞耐药机制研究 [J]. 中国临床药理学杂志 , 2021 , 37 ( 14 ): 1806 - 1810 .
班纪芳 , 客蕊 . 中药苏木抗肿瘤作用研究进展 [J]. 时珍国医国药 , 2020 , 31 ( 8 ): 1963 - 1967 .
戴凌虹 , 孙云 , 陈祥艳 . 莪术醇对人卵巢癌SKOV3细胞增殖、迁移、侵袭及凋亡的影响 [J]. 温州医科大学学报 , 2019 , 49 ( 10 ): 740 - 743 .
张铃 , 方翌 , 林久茂 , 等 . 半枝莲氯仿极性部位提取物调控linc01843逆转大肠癌5-FU耐药研究 [J]. 福建中医药 , 2021 , 52 ( 1 ): 23 - 27 .
刘浩 , 方素萍 , 张潇潇 . 扶正解毒方药调控T790M及c-Met改善吉非替尼获得性耐药 [J]. 世界中医药 , 2021 , 16 ( 8 ): 1221 - 1225 .
师林 , 黄圆圆 , 柯斌 . 加味龟鹿二仙胶汤联合顺铂对Lewis肺癌小鼠耐药相关基因及IL-7介导的Wnt/ β -catenin信号通路的影响 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 18 ): 66 - 72 .
PATEL N H , XU J , SALEH T , et al . Influence of nonprotective autophagy and the autophagic switch on sensitivity to cisplatin in non-small cell lung cancer cells [J]. Biochem Pharmacol , 2020 , doi: 10.1016/j.bcp.2020.113896 http://dx.doi.org/10.1016/j.bcp.2020.113896 .
HARRISON P T , VYSE S , HUANG P H . Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer [J]. Semin Cancer Biol , 2020 , 61 : 167 - 179 .
ROBICHAUX J P , ELAMIN Y Y , TAN Z , et al . Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer [J]. Nat Med , 2018 , 24 ( 5 ): 638 - 646 .
HUANG K , LIANG Q , ZHOU Y , et al . A novel allosteric inhibitor of phosphoglycerate mutase 1 suppresses growth and metastasis of non-small-cell lung cancer [J]. Cell Metab , 2019 , 30 ( 6 ): 1107 - 1119 .
冯燕 . PGAM1调控糖酵解流诱导卵巢癌细胞耐紫杉醇的机制研究 [D]. 杭州 : 浙江大学 , 2017 .
井元英 . 结肠癌采用奥沙利铂联合化疗治疗的疗效探究 [J]. 中国实用医药 , 2019 , 14 ( 33 ): 113 - 114 .
CHEN H , WANG X , GOU S . A cisplatin-based platinum (Ⅳ) prodrug containing a glutathione s-transferase inhibitor to reverse cisplatin-resistance in non-small cell lung cancer [J]. J Inorg Biochem , 2019 , 193 : 133 - 142 .
CHO S G , LEE Y H , PARK H S , et al . Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1 [J]. J Biol Chem , 2001 , 276 ( 16 ): 12749 - 12755 .
DROZD E , KRZYSZTOŃ-RUSSJAN J , MARCZEWSKA J , et al . Up-regulation of glutathione-related genes, enzyme activities and transport proteins in human cervical cancer cells treated with doxorubicin [J]. Biomed Pharmacother , 2016 , 83 : 397 - 406 .
ROCA J . The mechanisms of DNA topoisomerases [J]. Trends Biochem Sci , 1995 , 20 ( 4 ): 156 - 160 .
张游华 , 顾牣赜 , 牛天力 , 等 . DNA拓扑异构酶抑制剂在逆转肿瘤多药耐药性中的研究进展 [J]. 现代肿瘤医学 , 2016 , 24 ( 24 ): 4030 - 4033 .
LIAN C , CAO S , ZENG W , et al . RJT-101, a novel camptothecin derivative, is highly effective in the treatment of melanoma through DNA damage by targeting topoisomerase 1 [J]. Biochem Pharmacol , 2020 , doi: 10.1016/j.bcp.2019.113716 http://dx.doi.org/10.1016/j.bcp.2019.113716 .
姚娟 , 吴平安 , 李芸 , 等 . Keap1-Nrf2-ARE信号通路及其激活剂的研究进展 [J]. 中国药理学通报 , 2019 , 35 ( 10 ): 1342 - 1346 .
TKACHEV VO , MENSHCHIKOVA EB , ZENKOV NK . Mechanism of theNrf2/Keap1/ARE signaling system [J]. Biochemistry(Mosc) , 2011 , 76 ( 4 ): 407 - 422 .
GAO A M , KE Z P , SHI F , et al . Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway [J]. Chem Biol Interact , 2013 , 206 ( 1 ): 100 - 108 .
段俊伟 , 倪文 . NRF2/PI3K通路介导肝癌细胞SMMC-7721出现索拉非尼耐药的机制研究 [J]. 肝脏 , 2020 , 25 ( 9 ): 930 - 932,985 .
DAYA HA , KOUBA S , OULED-HADDOU H , et al . Orai3-mediates cisplatin-resistance in non-small cell lung cancer cells by enriching cancer stem cell population through PI3K/Akt pathway [J]. Cancers (Basel) , 2021 , 13 ( 10 ): 2314 .
HSU H H , KUO W W , SHIH H N , et al . FOXC1 regulation of miR-31-5p confers oxaliplatin resistance by targeting LATS2 in colorectal cancer [J]. Cancers (Basel) , 2019 , 11 ( 10 ): 1576 .
KONG S , Y CAO , LI X , et al . MiR16 sensitizes glioma cells to temozolomide by targeting FGFR1 and regulating the FGFR1/PI3K/Akt pathway [J]. J Cell Mol Med , 2020 , 24 ( 8 ): 4677 - 4686 .
王重植 , 易文君 . PTPRZ1通过调控PI3K/Akt通路促进乳腺癌细胞增殖和多西他赛耐药 [J]. 现代肿瘤医学 , 2020 , 28 ( 24 ): 4227 - 4231 .
ZHANG J , QU Z , YAO H , et al . An effective drug sensitizing agent increases gefitinib treatment by down regulating PI3K/Akt/mTOR pathway and up regulating autophagy in non-small cell lung cancer [J]. Biomed Pharmacother , 2019 , 118 : 109169 .
YU X , HUANG M , YANG G . Long non-coding RNA BANCR promotes proliferation, invasion and migration in esophageal squamous cell carcinoma cells via the Raf/MEK/ERK signaling pathway [J]. Mol Med Rep , 2021 , 23 ( 6 ): 465 .
LI J , YE T , LIU Y , KONG L , et al . Transcriptional activation of Gstp1 by MEK/ERK signaling confers chemo-resistance to cisplatin in lung cancer stem cells [J]. Front Oncol , 2019 , 9 : 476 .
ZHAO Z , ZHANG D , WU F , et al . Sophoridine suppresses lenvatinib-resistant hepatocellular carcinoma growth by inhibiting RAS/MEK/ERK axis via decreasing VEGFR2 expression [J]. J Cell Mol Med , 2020 , 25 ( 1 ): 549 - 560 .
CHEN K G , SIKIC B I . Molecular path ways: regulation and therapeutic implications of multidrug resistance [J]. Clin Cancer Res , 2012 , 18 ( 7 ): 1863 - 1869 .
ZHANG X Y , ZHANG Y K , WANG Y J , et a1 . Osimertinib (AZD9291), a mutant-selective EGFR inhibitor, reverses ABCB1-mediated drug resistance in cancer cells [J]. Molecules , 2016 , 21 ( 9 ): 1236 .
HSIAO S H , LU Y J , LI Y Q , et a1 . Osimertinib (AZD9291) attenuates the function of multidrug resistance-linked ATP-binding cassette transporter ABCB1 in vitro [J]. Mol Pharm , 2016 , 13 ( 6 ): 2117 - 2125 .
罗燕鸿 , 叶蕾 , 孔丹莉 , 等 . 高表达lncRNAs与肿瘤发生发展的相关性及其临床应用价值 [J]. 现代肿瘤医学 , 2016 , 24 ( 22 ): 3654 - 3659 .
CHANG L , HU Z , ZHOU Z , et al . Linc00518 contributes to multidrug resistance through regulating the MiR-199a/MRP1 axis in breast cancer [J]. Cell Physiol Biochem , 2018 , 48 ( 1 ): 16 - 28 .
王舒亚 , 滕雪 , 孔祥雪 , 等 . 长链非编码RNA在抗肿瘤药物耐药中的研究进展 [J]. 肿瘤学杂志 , 2019 , 25 ( 11 ): 995 - 1000 .
YUAN J , YIN Z , TAN L , et al . Interferon regulatory factor-1 reverses chemoresistance by downregulating the expression of P-glycoprotein in gastric cancer [J]. Cancer Lett , 2019 , 457 : 28 - 39 .
IKINK G J , HILKENS J . Insulin receptor substrate 4 (IRS4) is a constitutive active oncogenic driver collaborating with HER2 and causing therapeutic resistance [J]. Mol Cell Oncol , 2017 , 4 ( 2 ): e1279722 .
HUA X , ZHANG H , JIA J , et al . Roles of S100 family members in drug resistance in tumors: Status and prospects [J]. Biomed Pharmacother , 2020 , 127 : 110156 .
高静 . S100A4在卵巢癌顺铂耐药中的作用 [D]. 西安 : 第四军医大学 , 2012 .
许欣 . S100A4与卵巢癌铂类耐药的相关性研究 [D]. 西安 : 第四军医大学 , 2014 .
陈晓兰 , 丁颖 , 秦鑫 , 等 . 肿瘤源性S100A9对食管鳞癌细胞顺铂耐药性的影响 [J]. 广东医学 , 2015 , 36 ( 16 ): 2484 - 2487 .
王娅杰 , 李琦 , 李玉洁 , 等 . 中药在逆转肿瘤多药耐药中的作用及研究现状 [J]. 中国中药杂志 , 2014 , 39 ( 24 ): 4693 - 4698 .
徐栋 . 和厚朴酚逆转P-g介导的肿瘤多药耐药及协同、增敏化疗药物杀伤肿瘤细胞的体内外药效研究 [D]. 杭州 : 浙江大学 , 2007 .
刘文虎 , 袁江北 , 张帆 , 等 . 姜黄素通过Wnt3a/ β -catenin/EMT信号通路抑制胃癌细胞的增殖、迁移及侵袭 [J]. 中国中药杂志 , 2019 , 44 ( 14 ): 3107 - 3115 .
常娜 , 王小平 , 胥冰 . 姜黄素逆转肿瘤多药耐药机制的研究进展 [J]. 吉林中医药 , 2018 , 38 ( 11 ): 1359 - 1362 .
李雷 , 陈军 , 李贺 , 等 . 姜黄素干预的人结肠癌耐药细胞蛋白质组学分析 [J]. 山东医药 , 2018 , 58 ( 26 ): 18 - 22 .
JIANG X , HUANG Y . Curcumin derivative C086 combined with cisplatin inhibits proliferation of osteosarcoma cells [J]. Med Sci Monit , 2020 , doi: 10.12659/MSM.924507 http://dx.doi.org/10.12659/MSM.924507 .
王维兵 , 张林西 , 罗强 , 等 . 姜黄素逆转食管癌Eca-109/VCR细胞耐药性的研究 [J]. 中国临床药理学杂志 , 2021 , 37 ( 2 ): 136 - 139 .
牛天力 . 华蟾酥毒基联合多西他赛干预前列腺癌PC3细胞生长及耐药性的研究 [D]. 北京 : 北京中医药大学 , 2019 .
刘丽娜 , 李素梅 , 吴迪 , 等 . 芒柄花素抗肿瘤作用机制研究进展 [J]. 黑龙江医药 , 2017 , 30 ( 5 ): 953 - 956 .
李甜 , 唐润薇 , 袁帅 , 等 . 芒柄花素抑制自噬逆转激素受体阳性人乳腺癌细胞多药耐药的机制研究 [J]. 上海中医药杂志 , 2020 , 54 ( S1 ): 147 - 152 .
汤世民 , 邢小燕 , 邓雪红 , 等 . 冠心丹参方及其有效成分治疗冠心病的研究进展 [J]. 中国中药杂志 , 2016 , 41 ( 20 ): 3721 - 3726 .
颜晓静 , 杨烨 , 毕蕾 , 等 . 丹参-人参组分配伍对肺癌A549增殖、凋亡和骨架的影响 [J]. 中国中药杂志 , 2014 , 39 ( 22 ): 4436 - 4441 .
金忠明 , 洪伟鹏 , 黄民 , 等 . 丹参在逆转肿瘤耐药及化疗增敏中的研究进展 [J]. 中国药理学通报 , 2018 , 34 ( 7 ): 889 - 891 .
王蓉 , 马腾茂 , 刘飞 , 等 . 防己的药理作用及临床应用研究进展 [J]. 中国中药杂志 , 2017 , 42 ( 4 ): 634 - 639 .
张艺 . 防己中逆转非小细胞肺癌化疗耐药性有效成分的筛选及分子机制研究 [D]. 兰州 : 兰州大学 , 2019 .
陈雷 , 彭骁 , 胡兵 . 半枝莲抗肿瘤作用及临床应用研究进展 [J]. 新中医 , 2020 , 557 ( 10 ): 22 - 26 .
怀其娟 , 韩凤娟 , 王秀霞 , 等 . 中药复方理冲生髓饮对Casp-8和CXCL2基因在人卵巢癌细胞株SKOV3中表达的影响 [J]. 中国妇幼保健 , 2010 , 25 ( 12 ): 1689 - 1692 .
付杨 , 夏霁 , 韩凤娟 . 理冲生髓饮有效组分对卵巢癌干细胞调控相关基因及顺铂耐药性的影响及其作用机制研究 [J]. 中国全科医学 , 2019 , 22 ( 9 ): 1078 - 1083 .
田晓琳 , 张雅月 , 杨臻 , 等 . miRNA-17-92高表达白血病动物模型化疗敏感性及复方浙贝颗粒增敏作用研究 [J]. 白血病·淋巴瘤 , 2018 , 27 ( 4 ): 222 - 227 .
吕鹏 , 赵欢 , 石凤芹 , 等 . 复方浙贝颗粒联合顺铂对急性淋巴细胞白血病耐药细胞株移植瘤细胞耐药相关酶表达的影响 [J]. 中国中医药信息杂志 , 2019 , 26 ( 11 ): 52 - 56 .
马靖 , 王凤云 , 张佳琪 , 等 . 基于细胞信号通路探讨葛根芩连汤治疗溃疡性结肠炎的研究进展 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 17 ): 186 - 192 .
李雪莲 , 王嘉馨 , 王静 , 等 . 不同浓度葛根芩连水煎液对Caco-2细胞P-糖蛋白及多药耐药蛋白转运体表达的影响 [J]. 中国中药杂志 , 2018 , 43 ( 15 ): 3135 - 3139 .
文柳静 , 张洁 . 参芪扶正注射液通过调控miR-29b/Bcl-2通路逆转胰腺癌多药耐药研究 [J]. 中草药 , 2021 , 52 ( 14 ): 4262 - 4267 .
吴依芬 , 王刚 , 谭庆麟 , 等 . 补中益气汤通过SHP-1对转移性乳腺癌TAM耐药性的影响 [J]. 广东医学 , 2018 , 39 ( 12 ): 1776 - 1779,1785 .
0
Views
27
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621