microRNAs与ABC转运蛋白介导的肿瘤多药耐药研究进展

Association of microRNAs with tumor multi-drug resistance mediated by ABC transporter proteins

目的回顾ABC转运蛋白与肿瘤耐药的研究现状,探讨miRNA在逆转肿瘤耐药过程中的作用机制。方法应用PubMed和CNKI期刊全文数据库检索系统,检索2010-01-01-2014-05-20的相关文献,以"ABC转运蛋白、miRNA和多药耐药"为关键词。纳入标准:1)ABC转运蛋白的表达水平与肿瘤耐药;2)miRNA对ABC转运蛋白表达水平的调控;3)miRNA对肿瘤细胞药物敏感性的影响,根据纳入标准符合分析的文献34篇。结果大多数癌症患者使用一种化疗药物治疗后,肿瘤细胞可能因为种种原因,不仅对该药产生耐药,而且对多种结构不同和作用机制完全不同的其他药物也产生交叉耐药。研究表明,在多药耐药导致肿瘤化疗失败的众多原因中,ABC转运蛋白过表达是导致肿瘤多药耐药的主要原因之一。在耐药肿瘤细胞当中高表达的ABC转运蛋白主要有乳腺癌耐药蛋白ABCG2,多药耐药相关蛋白ABCC1,P-糖蛋白ABCB1,这些蛋白采用ATP水解的能量将细胞内药物泵出细胞外,从而降低细胞内药物的浓度,使细胞产生耐药性。miRNA能与ABC转运蛋白mRNA的3′UTR结合,使mRNA降解或抑制其翻译,导致目标蛋白的表达受到抑制,从而增加肿瘤细胞的药物敏感性,逆转由ABC转运蛋白过表达引起的肿瘤多药耐药。结论 miRNA可以逆转由ABC转运蛋白家族高表达所引起的肿瘤耐药,这为肿瘤多药耐药的研究提供了新的思路。

OBJECTIVE To review the evolution of ABC transport protein and tumor multi-drug resistance and dis- cuss the mechanism about miRNA reverse the tumor drug resistance. METHODS Searched with ＂ABC transport protein＂ and ＂miRNA＂ and ＂MDR＂ as key words within PubMed and CNKI database retrieval systems in recent 5 years（2010/1/ 1 2014/5/20）. Thirty-four papers were finally selected according to the inclusion criteria as follows： 1） the expression of ABC transport protein and tumor MDR; 2） miRNAs regulate the expression of ABC transport protein; 3） the influence of the drug sensitivity of miRNAs in cancer cells. RESULTS After treated with one chemotherapy drug,tumor cells may not only be resistant to the drug,but also be resistant to other drugs of different structures or mechanisms. Researches show that high ABC transporter level is one of the leading causes of tumor multi-drug resistance among all important reasons of multi-resistant leading to tumor chemotherapy failure. High expression of ABC transporters in drug-resistant tumor cells are breast cancer resistance protein ABCG2,multi-resistant related protein ABCC1 ,P-glycoprotein ABCB1, they contribute to reducing the concentration of the drug inside the cell, thereby developing resistance to anticancer drugs via ATP-de- pendent drug efflux, miRNA make the target mRNA degradation or inhibit its translation by targeting mRNA 3rUTR then the target protein is restrained and can reserve the tumor MDR mediated by up-regulation of ABC transport protein. CON- CLUSION miRNA can reserve the tumor MDR mediated by up-regulation of ABC transport protein,which may provide new thoughts for the research of tumor MDR.