Shimizu Takahiro, Fujii Takuto, Sakai Hideki
Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Front Cell Dev Biol. 2020 Oct 27;8:597835. doi: 10.3389/fcell.2020.597835. eCollection 2020.
Cisplatin [-diamminedichloroplatinum (II)] is a platinum-based anticancer drug widely used for the treatment of various cancers. It forms interstrand and intrastrand cross-linking with DNA and block DNA replication, resulting in apoptosis. On the other hand, intrinsic and acquired cisplatin resistance restricts its therapeutic effects. Although some studies suggest that dramatic epigenetic alternations are involved in the resistance triggered by cisplatin, the mechanism is complicated and remains poorly understood. Recent studies reported that cytoskeletal structures regulate cisplatin sensitivity and that activities of membrane transporters contribute to the development of resistance to cisplatin. Therefore, we focus on the roles of actin filaments and membrane transporters in cisplatin-induced apoptosis. In this review, we summarize the relationship between actin cytoskeleton and membrane transporters in the cisplatin resistance of cancer cells.
顺铂（-二氯二氨铂（II））是一种基于铂的抗癌药物，广泛用于治疗各种癌症。它与DNA形成链间和链内交联并阻断DNA复制，从而导致细胞凋亡。另一方面，内在性和获得性顺铂耐药性限制了其治疗效果。尽管一些研究表明，显著的表观遗传改变参与了顺铂引发的耐药性，但该机制复杂且仍知之甚少。最近的研究报道，细胞骨架结构调节顺铂敏感性，并且膜转运蛋白的活性有助于顺铂耐药性的产生。因此，我们关注肌动蛋白丝和膜转运蛋白在顺铂诱导的细胞凋亡中的作用。在这篇综述中，我们总结了肌动蛋白细胞骨架与膜转运蛋白在癌细胞顺铂耐药性中的关系。
