gms | German Medical Science

Background: Bile salts play an important pathogenic role in the development of Barrett adenocarcinoma (BA). However, the precise role of different bile salts in this process is still unknown. The aim of the present study was to compare the effects of two different bile salts, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on the expression of COX-2, CDX-2 and DNA repair enzymes (MUTYH, OGG1) in the Barrett epithelial cancer cells (OE-19).

Methods: OE-19 cells were incubated with DCA or UDCA (100µM or 300µM at pH=7.0) over 12 hours. To investigate the involvement of NFkappaB, in separate experiments the cells were incubated with DCA in the presence of proteosom inhibitor (MG-132). Cell survival was analyzed by MTT assay. After incubation of OE-19 cells with bile salts, the expression of mRNA of COX-2, DNA repair enzymes (MUTYH, OGG1) and caudal-related homebox transcription factor CDX2 was measured by quantitative RT-PCR .

Results: DCA caused a stronger reduction in cell survival of OE-19 cells than UDCA. In addition, DCA stimulated directly the translocation of NFkB p65 (active form) in the nuclei of OE-19 cells. DCA caused stronger than UDCA stimulation of the COX-2 mRNA expression in these cells and this effect was significantly attenuated by the addition of inhibitor of NFkappaB activity (proteosome inhibitor MG-132). DCA caused stronger downregulation of mRNA for DNA repair enzymes MUTYH and OGG1 than UDCA. In contrast, UDCA induced stronger CDX2 mRNA expression than DCA in OE-19 cells.

Conclusion: Bile salts are involved in the carcinogenesis of Barrett adenocarcinoma via inhibition of DNA repair enzymes and induction of COX-2 and this last effect is at least partly mediated by NFkappaB. UDCA promotes upregulation of CDX2 modulating development of Barrett carcinoma.