肿瘤多药耐药机制的研究进展  

The research progress on mechanisms of cancer multidrug resistance

作　　者：王庭丰 杜兴龙[1] 魏洁[1] 

机构地区：[1]滁州市第一人民医院肿瘤内科,安徽滁州239000

出　　处：《中华全科医学》2017年第6期1027-1031,共5页Chinese Journal of General Practice

基　　金：安徽省卫生和计划生育委员会科研计划项目(2016-QK008)

摘　　要：当前,恶性肿瘤是严重威胁人类健康和生命的疾病之一。在我国城镇居民人口中,肿瘤导致的死亡占各类疾病的25%。临床上治疗恶性肿瘤的常用方法有手术治疗、放疗和化疗3种治疗方案,其中化疗在恶性肿瘤治疗中占据着不可替代的位置。有些患者经过有效的化疗后仍会复发,其中最重要的原因就是肿瘤多药耐药(multidrug resistant,MDR)的产生限制了化疗的疗效。临床上应用联合化疗虽然能发挥最大的细胞毒作用,也因MDR的产生而失败。因此,克服肿瘤多药耐药是未来研究肿瘤治疗方法的关键。肿瘤多药耐药的产生是一个十分复杂的过程,受多种因素影响。肿瘤细胞通过多种途径导致多药耐药的产生,包括:耐药相关蛋白;DNA损伤和修复功能障碍;细胞自噬;减少药物积累和增加药物输出;代谢解毒;药物靶标和信号转导分子的改变等多种机制。肿瘤多药耐药与P-糖蛋白、乳腺癌耐药蛋白、多药耐药相关蛋白、肺耐药蛋白、拓扑异构酶以及细胞凋亡相关蛋白有关。目前有很多逆转剂应用于临床,但是疗效好、毒副作用小的MDR逆转剂还有待进一步研究。因此,对MDR机制的研究,并掌握癌细胞如何对抗癌药物产生抗性,将有助于研制出更加有效的抗肿瘤药物。本文现就国内外关于肿瘤细胞MDR产生的分子机制做一综述。Currently,malignancy is one of the serious threats to human health and life. In China＇s urban population,tumor-induced deaths account for 25% of all diseases. Clinical treatment of malignant tumors commonly used three kinds of methods of surgical treatment,radiotherapy and chemotherapy,chemotherapy play an irreplaceable role in the treatment of malignant tumors. Some patients after the effective chemotherapy will continue to relapse,the most important reason is that the formation of multidrug resistance（ MDR） to limit the efficacy of chemotherapy. Clinical application of combined chemotherapy can play the largest cytotoxic effect,but also because of the production of MDR failed. Therefore,overcome the multidrug resistance of tumors is an key to future research on tumor therapy. The mechanism of MDR is a very complicated process,influenced by many factors. Tumor cells cause multidrug resistance in a variety of ways,including drug-related proteins,DNA damage and repair dysfunction,cell autophagy,reduced drug accumulation and increased drug output,metabolic detoxification,drug targets and signal transduction molecules changes and other mechanisms. Tumor multidrug resistance is associated with P-glycoprotein,breast cancer resistance protein,multidrug resistance-associated protein,lung resistance protein,topoisomerase and apoptosis-related proteins. There are many reversal agent used in clinical,but the effective and toxic side effects of small MDR reversal agent remains to be further studied. Therefore,to study the mechanism of MDR and tumor cells produce resistance to drugs will be helpful to develop more effective antitumor drugs. This paper presents a review on the current research of molecular mechanism of MDR.

关 键 词：肿瘤 多药耐药 机制 进展 

分 类 号：R730[医药卫生—肿瘤]