PS02.044: A BARRETT’S CELL CULTURE MODEL, SHOWING AN INCREASED ACID TOLERABILITY OF ESOPHAGEAL ADENOCARCINOMA CELLS

Abstract

Abstract Background Inflammation is a common in esophageal adenocarcinoma (EAC). The response of EAC to common chemotherapeutic regimes is relatively low and the 5-years-survival is poor. The influence of acidic reflux on the viability of esophageal adenocarcinoma cells is unknown. Methods We investigated the influence of acidified medium conditions (pH3; pH3.5; pH4) in a Barrett's cell culture model, using six cell lines representing the Barrett's sequence from normal esophageal epithelium (EPC1 and EPC2), metaplasia (CP-A), dysplasia (CP-B) and EAC (OE33 and OE19) for their tolerability against an acid pulse of 15 and 30 min as well as expression profile of the Nrf2-Keap1-signalling pathway and their downstream targets. Results The Barrett's sequence was characterized by an increase of acid tolerability in the more advanced cells of this sequence. The squamous epithelium cell line EPC1 has shown the highest susceptibility with a decrease of 75% of cell viability, when treated with pH4 medium for 15min, while dysplastic and EAC cells had shown only a decrease of 10–25%. The lowest susceptibility was observed in the EAC cell line OE33, which had also 90% living cell in pH3 medium after 15min and had almost 30% living cells after 30min, when all other investigated cell lines showed no more living cells. Additionally, treatment with acidified medium was accompanied with an increase of the Nrf2 target gene hemeoxygensae-1. Conclusion We could show an increased tolerability against acidified medium (pH3) in cells representing advanced Barrett's esophagus stages, accompanied by an activation of Keap1-Nrf2-signalling pathway. However, acidic reflux may influence inflammation and chemo-sensitivity of the EAC. Disclosure All authors have declared no conflicts of interest.