COX-2 siRNA Strengthens The Anti-Proliferative Effects of Acid And Bile Salts on Human Esophageal Cells And Barrett Esophageal Cells

Abstract Aims: Investigating the effect and mechanism of COX-2 on viability, intestinal metaplasia, and atypia of human esophageal squamous and Barrett esophageal cell lines. Methods: Human esophageal squamous and Barrett esophageal cell lines were transfected with COX-2 expression vector and COX-2 siRNA, then were treated with acid, bile salts, and a mixture of both. Cell viability, the expression of COX-2, NF-κB, CDX-2, MUC2 and BMP-4, and the morphology and microstructure of cells were observed. Results: The viability of the COX-2 over expressed cells was significantly higher than that of the control cells, while the viability of the COX-2 siRNA-treated cells was significantly lower than that of the control cells. The intestinal metaplasia and atypia were observed in cells over expressing COX-2. Acid, bile salts, and their mixture inhibited the viability of the two cell lines, but the inhibitory effect of the mixture was stronger than single treatment with either. siRNA of COX-2 strengthened the anti-proliferative effects of the mixture on Het-1A and BAR-T cells. Expression of NF-κB, CDX-2 and BMP-4 was positively correlated with COX-2 expression. Conclusion: COX-2 may influence the viability, atypia and intestinal metaplasia of human esophageal cells and Barrett esophageal cells. Activation of NF-κB, CDX-2, and BMP-4 signaling pathway by COX-2 may be part of the mechanisms.