Bile Acid Induces Cyclo‐Oxygenase‐2 Expression in Cultured Human Pharyngeal Cells: A Possible Mechanism of Carcinogenesis in the Upper Aerodigestive Tract by Laryngopharyngeal Reflux

Abstract

Laryngopharyngeal reflux is a common event in patients with head and neck cancer. Bile acid is known to be related to tumor formation in the esophagus through the overexpression of cyclo-oxygenase-2 (COX-2), an enzyme that produces prostanoids. To better understand the mechanism of the laryngopharyngeal reflux-cancer connection, we examined COX-2 expression by bile acid in cultured human pharyngeal mucosa cells. COX-2 expression induction by various combinations of chenodeoxycholate and acidity was observed by Western blotting and reverse transcriptase-polymerase chain reaction. COX-2 promoter activity was also measured by luciferase promoter assay. Chenodeoxycholate, one of the bile acid components, was found to induce COX-2 expression in human pharyngeal cells. Moreover, the induction of COX-2 by chenodeoxycholate was enhanced by acidity in a dose-dependent manner, and the promoter activity of COX-2 was increased by chenodeoxycholate in SNU-1041, a human laryngeal cancer cell line, whereas the transcription of COX-2 was inhibited by actinomycin-D. Bile salts or acidic conditions, or both, can induce COX-2 expression in normal pharyngeal mucosa, which implies that laryngopharyngeal reflux has a role in the tumorigenesis of the upper aerodigestive tract.