孕烷X受体介导的代谢酶和转运体转录调控及其在化疗药物耐药中的作用

摘要/Abstract

摘要： 孕烷X受体(PXR, NR1I2)是生物体内药物代谢酶和转运体基因表达的主要调控因子之一。近来研究发现,PXR介导的药物代谢酶和转运体的过表达,与化疗药物多药耐药的产生密切相关。鉴于PXR在药物代谢酶和转运体调控中的重要性和PXR转录调控的多样性,有必要对其导致的多药耐药形成机制进行更深入的研究。本文综述了PXR介导的代谢酶和转运体基因表达调控机制,及其引起化疗药物多药耐药的相关研究进展,为提高化疗药物敏感性、逆转化疗药物的多药耐药提供有效的治疗策略。

关键词: 孕烷X受体, 转运体, 代谢酶, 转录调控, 化疗药物, 多药耐药

Abstract: The pregnane X receptor (PXR, NR1I2) is a key member of the nuclear receptor superfamily that has been shown to mediate the transcriptional regulation of drug metabolism enzymes and transporters. Recent studies have shown that overexpression of drug metabolism enzymes and transporters induced by active PXR correlated to the multidrug resistance of chemotherapeutic agents. It is urgent to reveal the underling mechanism of multidrug resistance mediated by PXR in light of the fact that PXR is extensively involved in the transcriptional regulation of drug metabolism enzymes and transporters. This review summarizes the latest studies about the mechanisms of transcriptional regulation of drug metabolism enzymes and transporters by PXR, and their roles in multidrug resistance of chemotherapeutic agents, for providing an effective therapeutic strategy for enhancing sensitivity of chemotherapeutic agents and attenuating multidrug resistance.

Key words: Pregnane X receptor, Transporter, Metabolism enzyme, Transcriptional regulation, Chemotherapeutic agents, Multidrug resistance

中图分类号:

R969. 2

赵其锦, 査伟斌, 周芳, 吴晓兰, 曹蓓, 张经纬, 王广基. 孕烷X受体介导的代谢酶和转运体转录调控及其在化疗药物耐药中的作用[J]. 中国临床药理学与治疗学, 2012, 17(8): 931-939.

ZHAO Qi-jin, ZHA Wei-bin, ZHOU Fang, WU Xiao-lan, CAO Bei, ZHANG Jing-wei, WANG Guang-ji. The transcriptional regulation of drug enzymes and transporters mediated by Pregnane X receptor and its significant role in multidrug resistance[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(8): 931-939.

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