The transcriptional regulation of drug enzymes and transporters mediated by Pregnane X receptor and its significant role in multidrug resistance

Abstract

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

CLC Number:

R969. 2

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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