Chemoprevention targeting bile acid receptor for esophageal adenocarcinoma

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Gastroesophageal reflux of bile acid is associated with the development of Barrett's epithelium and thereafter adenocarcinoma. Although bile acids are reported to activate farnesoid X recepor that is one of the nuclear hormone receptors, it is unknown whether its signaling is involved in the development of Barrett's adenocarcinoma. In this study, we examined the effects of guggulsterone, a farnesoid X receptor antagonist, on the signaling pathway, especially Cdx2 expression in esophageal epithelial cells in vitro. Treatment with DCA and CDCA for 24 h increased the Cdx2 expression in Barrett's adenocarcinoma cells. Guggulsterone decreased not only basal Cdx2 expression but also DCA-or CDCA-induced Cdx2 expression. Bile acid-activating signaling pathways of farnesoid X receptor may be novel drug targets to prevent the development of Barrett's adenocarcinoma.