Pregnane X receptor and multidrug resistance / 国际药学研究杂志

ABSTRACT

Multidrug resistance(MDR) is the leading cause of treatment failure in cancer therapy. Overexpression of the ATP-binding cassette (ABC) transporter family increases the cellular efflux, decreases the effectiveness of chemotherapeutic agents,and results in MDR. In particular,overexpression of P-glycoprotein and its encoding genes(mdr1) is the major mechanism. It is feasible for overcoming MDR by studying the factors affecting mdr1 gene expression so as to block the expression of mdr1. Pregnane X receptor(PXR) can regulate the expression of MDR proteins, suggesting that it be possible to overcome drug resistance by regulating PXR. In this paper,the relation between PXR and MDR and recent development of PXR antagonists to pharmacologically modulate PXR are reviewed. The review proposes that selectively preventing the elevation of MDR levels by regulating PXR rather than non-selectively inhibiting the MDR activity by using MDR inhibitors can be a less toxic approach to overcome drug resistance during cancer therapy.