The role of intestinal human pregnane X receptor (PXR) in colon cancer was determined through investigation of the chemopreventive role of rifaximin, a specific agonist of human PXR, towards azoxymethane (AOM)/dextran sulfate sodium (DSS)–induced colon cancer. In this study, rifaximin treatment significantly decreased the numbers of colon tumors induced by AOM/DSS treatment in PXR humanized mice, but not in wild-type and Pxr-null mice. Nuclear factor κ-light chain enhancer of activated B cells–mediated inflammatory signaling was upregulated in AOM/DSS treated mice, and was inhibited by rifaximin in PXR-humanized mice. Cell proliferation and apoptosis were also modulated by rifaximin treatment in the AOM/DSS model. These results suggested that specific activation of intestinal human PXR exhibited a chemopreventive role towards AOM/DSS-induced colon cancer through mediating anti-inflammation, antiproliferation, and proapoptotic events.
See article at J Pharmacol Exp Ther 2014, 351:559–567.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics