多药耐药基因MDR 1 和细胞自噬在 肿瘤多重耐药机制中的研究进展

Role of MDR1 in multiple drug resistance in cancer

摘要:

肿瘤是威胁人类健康的恶性疾病。化疗是目前临床抗肿瘤最常用的治疗方法，化疗药物具有 较广的抗瘤谱。但肿瘤多重耐药的发生是导致化疗疗效不佳的主要原因。肿瘤多重耐药机制非常复杂，与 药物代谢、药物靶点改变、DNA 修复增强、细胞周期改变及肿瘤微环境等均有密切联系。其中多药耐药基 因MDR 1 表达的膜转运蛋白P- 糖蛋白参与的化疗药物逆向转用是多药耐药发生的重要机制之一，但是针 对MDR 1 的一些抑制剂并不能很好地解决肿瘤的耐药问题。近年来研究发现，细胞自噬直接参与肿瘤多药耐 药，联合调控MDR 1 的表达及肿瘤细胞自噬水平将可能改善肿瘤细胞的多重耐药。该文主要从多药耐药基因 MDR1 的表达调控及细胞自噬水平改变两方面综述肿瘤细胞多重耐药机制的研究进展。

Abstract:

Cancer is the most common malignant disease, and chemotherapy still plays a critical role in treatment of cancer. Multidrug resistance, however, significantly compromises therapeutic efficacy of chemotherapy. Mechanisms involved in multiple resistance is related to drug metabolism, target switch of drugs, enhanced capability of DNA repair and tumor microenvironment. P-Glycoprotein/MDR1 facilitates the efflux of various anticancer drugs, and is one of the most important mechanism in multidrug resistance, though MDR1 inhibitors is incapable of diminishing the multidrug resistance. Recent studies have reported that cell autophagy is directly involved in multidrug resistance. Combined regulation of MDR1 expression and autophagy activity may potentially overcome the issue. Therefore, this article reviews the progress in the study of mechanisms in multidrug resistance. This reviews targets two aspects: regulation of MDR1 expression, and autophagy activity in tumor cells.