Yuan Hongyu, Li Xun, Wu Jifeng, Li Jinpei, Qu Xianjun, Xu Wenfang, Tang Wei
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Jinan, Shandong Province, PR China.
Curr Med Chem. 2008;15(5):470-6. doi: 10.2174/092986708783503258.
Cancer patients who receive chemotherapy often experience intrinsic or acquired resistance to a broad spectrum of chemotherapeutic agents. The phenomenon, termed multidrug resistance (MDR), is often associated with the over-expression of P-glycoprotein, a transmembrane protein pump, which can enhance efflux of a various chemicals structurally unrelated at the expense of ATP depletion, resulting in decrease of the intracellular cytotoxic drug accumulation. The MDR has been a big threaten to the human health and the war fight for it continues. Although several other mechanisms for MDR are elucidated in recent years, considerable efforts attempting to inverse MDR are involved in exploring P-glycoprotein modulators and suppressing P-glycoprotein expression. In this review, we will report on the recent advances in various strategies for overcoming or circumventing MDR mediated by P-glycoprotein.
接受化疗的癌症患者常常对多种化疗药物产生内在性或获得性耐药。这种现象被称为多药耐药（MDR），通常与一种跨膜蛋白泵P-糖蛋白的过度表达有关，P-糖蛋白可增强多种结构不相关化学物质的外排，代价是ATP消耗，导致细胞内细胞毒性药物积累减少。多药耐药一直是对人类健康的重大威胁，针对它的斗争仍在继续。尽管近年来阐明了其他几种多药耐药机制，但为逆转多药耐药所做的大量努力都集中在探索P-糖蛋白调节剂和抑制P-糖蛋白表达上。在本综述中，我们将报告克服或规避由P-糖蛋白介导的多药耐药的各种策略的最新进展。
