抗癌药物顺铂的细胞蓄积：综述
Cellular accumulation of the anticancer agent cisplatin: a review.
作者信息
Gately D P, Howell S B
机构信息
Department of Biomedical Sciences, University of California, San Diego, La Jolla 92093-0812.
出版信息
Br J Cancer. 1993 Jun;67(6):1171-6. doi: 10.1038/bjc.1993.221.
Abstract
Acquired resistance to cisplatin (DDP) is a major clinical problem in the treatment of ovarian, testicular, and head and neck carcinomas; decreased accumulation of DDP is the most consistently observed alteration in resistant cells. It has been postulated that DDP enters the cell by passive diffusion based on the observations that DDP accumulation is proportional to the drug concentration, accumulation is not saturable, and that structural analogs of DDP do not inhibit accumulation. However, recent studies show that DDP accumulation can be specifically stimulated or inhibited by pharmacological agents and the activation of signal transduction pathways. This paper reviews the existing data on the mechanism of DDP accumulation and develops the postulate that some component of transport occurs through a gated ion channel.
摘要
顺铂（DDP）获得性耐药是卵巢癌、睾丸癌和头颈癌治疗中的一个主要临床问题；顺铂积累减少是耐药细胞中最常观察到的改变。基于顺铂积累与药物浓度成正比、积累不饱和以及顺铂结构类似物不抑制积累等观察结果，推测顺铂通过被动扩散进入细胞。然而，最近的研究表明，药理试剂和信号转导途径的激活可特异性地刺激或抑制顺铂积累。本文综述了关于顺铂积累机制的现有数据，并提出假说：转运的某些成分是通过门控离子通道进行的。
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