Activation of intestinal human pregnane X receptor protects against azoxymethane/dextran sulfate sodium-induced colon cancer

Jie Cheng, Zhong Ze Fang, Kenjiro Nagaoka, Minoru Okamoto, Aijuan Qu, Naoki Tanaka, Shioko Kimura, Frank J. Gonzalez

研究成果査読

17 被引用数 (Scopus)

抄録

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 intestinal human PXR, toward azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon cancer. Rifaximin treatment significantly decreased the number of colon tumors induced by AOM/DSS treatment in PXR-humanized mice, but not wild-type or Pxr-null mice. Additionally, rifaximin treatment markedly increased the survival rate of PXR-humanized mice, but not wild-type or Pxr-null mice. These data indicated a human PXR-dependent therapeutic chemoprevention of rifaximin toward AOM/DSS-induced colon cancer. Nuclear factor k-light-chain-enhancer of activated B cells -mediated inflammatory signaling was upregulated in AOM/DSS-treated mice, and inhibited by rifaximin in PXRhumanized mice. Cell proliferation and apoptosis were also modulated by rifaximin treatment in the AOM/DSS model. In vitro cell-based assays further revealed that rifaximin regulated cell apoptosis and cell cycle in a human PXR-dependent manner. These results suggested that specific activation of intestinal human PXR exhibited a chemopreventive role toward AOM/DSS-induced colon cancer by mediating anti-inflammation, antiproliferation, and proapoptotic events.

本文言語English
ページ(範囲)559-567
ページ数9
ジャーナルJournal of Pharmacology and Experimental Therapeutics
351
3
DOI
出版ステータスPublished - 12月 1 2014
外部発表はい

ASJC Scopus subject areas

  • 分子医療
  • 薬理学

フィンガープリント

「Activation of intestinal human pregnane X receptor protects against azoxymethane/dextran sulfate sodium-induced colon cancer」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル