Department of Chemistry, University of Bari, via Orabona, 4, 70125 Bari, Italy.
Department of Chemistry, University of Bari, via Orabona, 4, 70125 Bari, Italy.
Semin Cancer Biol. 2021 Nov;76:173-188. doi: 10.1016/j.semcancer.2021.05.023. Epub 2021 May 29.
Cisplatin, or cis-diamminedichloridoplatinum(II) cis-[PtCl(NH)], is a platinum-based anticancer drug largely used for the treatment of various types of cancers, including testicular, ovarian and colorectal carcinomas, sarcomas, and lymphomas. Together with other platinum-based drugs, cisplatin triggers malignant cell death by binding to nuclear DNA, which appears to be the ultimate target. In addition to passive diffusion across the cell membrane, other transport systems, including endocytosis and some active or facilitated transport mechanisms, are currently proposed to play a pivotal role in the uptake of platinum-based drugs. In this review, an updated view of the current literature regarding the intracellular transport and processing of cisplatin will be presented, with special emphasis on the plasma membrane copper permease CTR1, the Cu-transporting ATPases, ATP7A and ATP7B, located in the trans-Golgi network, and the soluble copper chaperone ATOX1. Their role in eliciting cisplatin efficacy and their exploitation as pharmacological targets will be addressed.
顺铂，或顺式二氨二氯合铂(II)顺-[PtCl(NH₃)]，是一种基于铂的抗癌药物，主要用于治疗各种类型的癌症，包括睾丸癌、卵巢癌和结直肠癌、肉瘤和淋巴瘤。顺铂与其他基于铂的药物一起，通过与核 DNA 结合触发恶性细胞死亡，这似乎是最终的靶标。除了通过细胞膜的被动扩散外，目前还提出其他转运系统，包括内吞作用和一些主动或促进转运机制，在铂类药物的摄取中发挥关键作用。在这篇综述中，将呈现关于顺铂细胞内转运和加工的当前文献的最新观点，特别强调位于反式高尔基体网络中的质膜铜渗透酶 CTR1、Cu 转运 ATP 酶 ATP7A 和 ATP7B 以及可溶性铜伴侣 ATOX1。将讨论它们在引发顺铂疗效中的作用及其作为药理靶点的利用。
