肝癌化疗耐药机制及中药干预研究进展  

Mechanism of Chemotherapy Resistance of Hepatocellular Carcinoma and Intervention with Chinese Medicine:A Review

作　　者：胡泽玉 杨清瑞 周铖 杨林 肖海娟[1,4] 方瑜 HU Zeyu;YANG Qingrui;ZHOU Cheng;YANG Lin;XIAO Haijuan;FANG Yu(Shaanxi University of Chinese Medicine,Xianyang 712046,China;The First Clinical Medical College of Henan University of Chinese Medicine,Zhengzhou 450046,China;Xianyang Central Hospital,Xianyang 712000,China;The Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China)

机构地区：[1]陕西中医药大学,陕西咸阳712046 [2]河南中医药大学第一临床医学院,郑州450046 [3]咸阳市中心医院,陕西咸阳712000 [4]陕西中医药大学附属医院,陕西咸阳712000

出　　处：《中国实验方剂学杂志》2022年第14期254-261,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：陕西省自然科学基金青年项目(2018JQ8014);陕西中医药大学创新团队项目(2019-YL06)。

摘　　要：多药耐药(MDR)是恶性肿瘤患者化疗失败的重要原因,也是提高患者生存质量,延长生存期等方面的瓶颈。肝癌细胞作为一种先天性耐药的肿瘤细胞,普遍对放化疗不敏感,且肝癌患者早期症状缺乏典型性,多数患者确诊已为晚期,生存期短,复发率高,随之而来的对化疗药物敏感性降低,继之MDR成为原发性肝癌(PHC)治疗失败的重要原因之一。因此,寻找安全、不良反应小、疗效佳的化疗增敏剂已成为肝癌耐药研究中需迫切解决的问题。随着中药在肿瘤疾病治疗的广泛应用,中药复方、中药注射液、中药单体在逆转肝癌化疗耐药方面机制研究也日益增加。基于中药研究现状,通过查阅相关文献数据库,其机制可概括为增加细胞内药物浓度、影响酶类物质活性变化、诱导细胞凋亡,逆转细胞信号通路异常、调控肿瘤微环境等。传统中医药从多靶点、多途径的角度减轻了肝癌细胞化疗耐药,增加了肝癌细胞的化疗敏感性以及化疗药物对肝癌细胞的毒性作用,因此,从中医药角度探讨肝癌MDR作用机制,对于逆转肝癌MDR具有重要意义,同时也为临床治疗肝癌提供参考价值。然而目前研究存在实验类型较单一,不良反应等不足,因而在未来需要从实验室到临床进行多机制,多靶点的实验研究及临床验证。Multidrug resistance(MDR)has been a main culprit behind the failure of chemotherapy in patients with malignant tumors and a major obstacle to improving the life quality and prolonging the survival of patients. Hepatocellular carcinoma cells,the innate drug-resistant cells,are generally insensitive to radiotherapy and chemotherapy. Moreover,as the early symptoms of hepatocellular carcinoma are atypical,most patients are diagnosed at the advanced stage,with short survival period and high recurrence rate. Thus,the sensitivity to chemotherapy drugs is decreased. This explains how MDR becomes one of the important reasons for the failure of primary hepatocellular carcinoma(PHC)treatment. Therefore,it is an urgent task to search for safe and effective chemosensitizers with little adverse effect in the research on the drug resistance of hepatocellular carcinoma. As Chinese medicine has been widely applied in the treatment of tumors,the mechanisms of compound Chinese medicine prescriptions, Chinese medicine injections, and single Chinese medicinal in reversing chemotherapy resistance in liver cancer have attracted the interest of scholars. According to previous reports,the mechanisms can be summarized as increasing intracellular drug concentration,influencing changes in enzyme activity,inducing apoptosis,reversing abnormalities in cellular signaling pathways,and regulating the tumor microenvironment. Traditional Chinese medicine reduces the chemotherapy resistance of hepatocellular carcinoma cells through multiple targets and multiple pathways,thereby improving the chemotherapy sensitivity of the cancer cells and enhancing the toxicity of chemotherapeutic drugs to hepatocellular carcinoma cells.Therefore,exploring the mechanism of MDR of hepatocellular carcinoma from the perspective of traditional Chinese medicine is important for reversing the MDR and is of great reference value for clinical treatment of hepatocellular carcinoma. However,there are few experimental types and adverse effects available. Thus,the multi-mecha

关 键 词：中医药 原发性肝癌 化疗耐药 逆转机制 多药耐药 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学] R2-031R735.7R285.5