OBJECTIVES: The incidence of esophageal adenocarcinoma is increasing in the United States. Frequent gastroesophageal reflux or gastroesophageal reflux disease, resulting in Barrett esophagus, may be responsible for the increase. In the present study, we determined the carcinogenic effects of bile acid in esophageal cancer and then explored the use of the farnesoid X receptor (FXR) inhibitor guggulsterone to control tumor cell viability and gene expression. METHODS: Cell culture, Western blot, RT-PCR, gene transfection, and immunohistochemistry assays were used. RESULTS: We found that bile acid inhibited RAR-β2 and RRIG1 but induced COX-2 expression in a dose- and time-dependent manner and that FXR, the bile acid receptor, was responsible. Furthermore, bile acid also induced FXR expression in esophageal cancer cell lines. Knockdown of FXR expression using FXR shRNA antagonized the effects of bile acid in gene expression. We then demonstrated that guggulsterone treatment was able to reduce the viability of esophageal cancer cells and induce RAR-β2 and RRIG1 expression but suppress COX-2 and MMP-9 expression. In addition, ex vivo data demonstrated that FXR was highly expressed in both esophageal squamous cell carcinoma (71%) and adenocarcinoma (81%) tissues and was associated with reduced RAR-β2 and RRIG1 expression. CONCLUSIONS: Suppression of FXR activity using FXR shRNA or its inhibitor guggulsterone was able to antagonize bile acid in regulating gene expression and cancer viability.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5676.

©2010 American Association for Cancer Research
2010