The multidrug transporter, a double-edged sword.
The multidrug transporter, a double-edged sword.
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多药转运蛋白是一把双刃剑。
DOI：
10.1016/s0021-9258(18)37730-5
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
I. Pastan
中科院分区：
文献类型：
--
作者：
M. Gottesman;I. Pastan
肿瘤细胞对强效化疗药物的毒性作用产生耐药性的途径的阐明，揭示了大量关于药物摄取、代谢和挤压的机制，并提供了对基因表达和基因扩增调节等细胞过程的基本见解。细胞生物学家和肿瘤学家面临的一个令人困惑的问题是，患者的培养细胞和肿瘤同时对多种化学无关的天然产物来源的化疗药物表现出耐药性的趋势。几个实验室最近的工作表明，这种多药耐药是由于一种多药转运蛋白，称为p糖蛋白或P170，它是由人类MDRl基因编码的（也见参考文献1-4）。这种多药转运体直接利用ATP的能量从细胞中挤出多种药物。在组织培养中选择多药耐药的细胞中鉴定出这种转运蛋白，使得开始检查正常组织中多药转运蛋白的功能成为可能。如下所述。G综述，这种转运蛋白的表达被确定为癌细胞耐药的一种机制，显然也可以作为一种保护动物免受饮食中有毒物质侵害的手段。
The elucidation of the means by which tumor cells develop resistance to the toxic effects of potent chemotherapeutic agents has revealed a great deal about mechanisms of drug uptake, metabolism, and extrusion, as well as providing basic insights into cellular processes such as regulation of gene expression and gene amplification. One perplexing problem facing the cell biologist and oncologist has been the tendency of cultured cells and tumors in patients to exhibit simultaneous resistance to multiple chemically unrelated chemotherapeutic agents that are of natural product origin. Recent work from several laboratories has shown that this multidrug resistance is due to a multidrug transport protein, known as P-glycoprotein or P170, which is encoded by the MDRl gene in the human (also reviewed in Refs. 1-4). This multidrug transporter directly uses the energy of ATP to extrude a large variety of drugs from cells. The identification of this transport protein in cells selected for multidrug resistance in tissue culture has made it possible to begin to examine the function of the multidrug transporter in normal tissues. As detailed in the fo1lowir. g review, this transporter, whose expression was identified as a mechanism of drug resistance in cancer cells, apparently may also function as a means of protecting animals against toxic substances present in their diets.