活性氧对P-糖蛋白调节作用的研究进展

Research progress on regulation of P-glycoprotein by reactive oxygen species

P-糖蛋白是由多药耐药基因(MDR1)编码的跨膜糖蛋白,介导ATP依赖的多药耐药,能把多种亲脂性外源物质排出胞外。P-gp过表达介导的多药耐药是目前多药耐药发生的主要机制。活性氧(reactive oxygen species,ROS)是细胞内的信号分子,能被多种物质调节升高。近有研究显示多种ROS诱导剂可以下调P-gp的表达,推测某些ROS诱导剂有望成为P-gp抑制剂而成为肿瘤多药耐药逆转剂研究的新方向。

P-glycoprotein（P-gp） encoded by multidrug resistance type 1（MDR1） genes mediates ATP-dependent efflux of numerous lipophilic xenobiotics,including several anticancer drugs,from cells.Overexpression of P-gp in tumour cells contributes to a multidrug resistance phenotype.Reactive oxygen species（ROS） is the signaling molecules in cells,and the levels of ROS are increased when exposed to various stress agents. Some studies have showed that intrinsic expression of P-glycoprotein may be down-regulated by ROS.So the compounds which can increase the level of ROS may reverse the type of MDR and the excitomotory of ROS will become the focuses of MDR reversal agents.