铜转运蛋白调节细胞药理学以及对铂类药物的敏感性。
Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs.
作者信息
Safaei Roohangiz, Howell Stephen B
机构信息
Department of Medicine and the Rebecca and John Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0058, USA.
出版信息
Crit Rev Oncol Hematol. 2005 Jan;53(1):13-23. doi: 10.1016/j.critrevonc.2004.09.007.
Recent studies have demonstrated that the major Cu influx transporter CTR1 regulates tumor cell uptake of cisplatin (DDP), carboplatin (CBDCA) and oxaliplatin (L-OHP), and that the two Cu efflux transporters ATP7A and ATP7B regulate the efflux of these drugs. Evidence for the concept that these platinum (Pt) drugs enter cells and are distributed to various subcellular compartments via transporters that have evolved to manage Cu homeostasis includes the demonstration of: (1) bidirectional cross-resistance between cells selected for resistance to either the Pt drugs or Cu; (2) parallel changes in the transport of Pt and Cu drugs in resistant cells; (3) altered cytotoxic sensitivity and Pt drug accumulation in cells transfected with Cu transporters; and (4) altered expression of Cu transporters in Pt drug-resistant tumors. Appreciation of the role of the Cu transporters in the development of resistance to DDP, CBDCA, and L-OHP offers novel insights into strategies for preventing or reversing resistance to this very important family of anticancer drugs.
最近的研究表明，主要的铜离子流入转运体CTR1调节肿瘤细胞对顺铂（DDP）、卡铂（CBDCA）和奥沙利铂（L-OHP）的摄取，而两种铜离子流出转运体ATP7A和ATP7B调节这些药物的流出。这些铂（Pt）类药物通过进化来维持铜稳态的转运体进入细胞并分布到各种亚细胞区室，这一概念的证据包括：（1）对铂类药物或铜产生抗性的细胞之间的双向交叉抗性；（2）抗性细胞中铂和铜药物转运的平行变化；（3）转染了铜转运体的细胞中细胞毒性敏感性和铂药物积累的改变；（4）铂类药物耐药肿瘤中铜转运体表达的改变。认识到铜转运体在对DDP、CBDCA和L-OHP耐药性发展中的作用，为预防或逆转对这一非常重要的抗癌药物家族的耐药性策略提供了新的见解。
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