Mo1852 Statin Use Reduces the Risk of Esophageal Cancer: A Meta-Analysis

Abstract

Background and Aim: Chronic inflammation has an important role by generating reactive oxygen species (ROS) in the development and progression of esophageal adenocarcinoma(EAC). Deoxycholic acid (DCA), causing chronic inflammation, plays the most significant role in the development of carcinogenesis during reflux. But the pro-inflammation of DCA in EAC cells is unknown. Adiponectin has anti-inflammatory and anti-tumor effects, but the mechanism of adiponectin in inflammation has not been very clear, especially in the development and progression of EAC. In this study, we aimed to observe the effect of two different type adiponectin, full-length adiponectin (f-Ad) and globular adiponectin (g-Ad), on the inflammatory response induced by DCA in EAC. Methods: OE19 cells were treated with DCA(50~300μM) or(and) f-Ad/g-Ad(10.0μg/ml). The cell viability was measured using MTT assay. Inflammatory factors were assayed by real-time PCR and ELISA analysis. The intra-cellular ROS levels were assayed using Flow Cytometry technology. Phosphor-nuclear factor kappaB (p-NF-κB) p65 protein was measured by Western blot. Results: High dose DCA (≥200μM) could significantly induce cytotoxicity and upregulate both mRNA and protein level of inflammatory factors TNF-α, IL-8 and IL-6 compared to untreated control in EAC cells. DCA(200μM) could apparently induce the release of ROS and increasing of p-NF-κBp65 protein. f-Ad suppressed DCA-induced the production of TNF-α, IL-8 and IL6 cytokines. Additionally, f-Ad also decreased DCA-induced the production of ROS and the p-NF-κBp65 protein. In contrast, g-Ad might further enhance DCA-induced inflammatory factors TNF-α, IL-8 and IL-6 production, and also increase intra-cellular ROS levels and pNF-κBp65 protein expression generated by DCA. Therefore, different type adiponectin differently regulate DCA-induced the inflammatory response by changing the ROS levels through NF-κBp65 activation. Conclusion: DCA exerts pro-inflammatory effect in a ROSNF-κBp65 dependent manner in EAC cells. f-Ad has an anti-inflammatory effect, whereas g-Ad appears to have an pro-inflammatory effect via changing the intra-cellular ROS levels, indicating that f-Ad could be a new potential anti-inflammatory reagent for cancer therapy.