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FXR影响结直肠癌发生发展的研究进展
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Abstract:
法尼醇X受体(Farnesoid X receptor, FXR)作为核受体超家族成员，是治疗代谢性疾病的潜在药物靶点。近来研究显示，FXR与结直肠癌(Colorectal cancer, CRC)的发生具有很强的相关性，FXR缺失与CRC进展呈正相关，肠道FXR的选择性激活可以限制异常Lgr5+细胞的生长并抑制CRC的进展，FXR的缺失也可以导致Wnt信号活化。同时，FXR也是胆汁酸(Bile acids, Bas)受体，BAs的结合会产生不同的FXR构象，调节各个FXR靶标的表达。肠选择性FXR激动剂在CRC的治疗中有一定的应用前景。本文就FXR对CRC发生的影响以及FXR激动剂在CRC治疗的相关进展作一综述。
Farnesoid X receptor (FXR), as a member of the nuclear receptor superfamily, is a potential drug target for the treatment of metabolic diseases. Recent studies show that FXR has a strong correlation with the occurrence of Colorectal cancer (CRC), and the deletion of FXR is positively correlated with the progression of CRC. Selective activation of FXR in gut can restrict the growth of abnormal Lgr5+ cells and inhibit the progression of CRC. The absence of FXR can also lead to activation of Wnt signaling. FXR is also a receptor for Bile acids (BAs), and the binding of BAs can produce different FXR conformations and regulate the expression of each FXR target. Intestinal selective FXR agonists have a promising application in the treatment of CRC. This article reviews the effect of FXR on the occurrence of CRC and the progress of FXR agonists in the treatment of CRC.
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