M1179 Targeting Epidermal Growth Factor Receptor With Polyethylene Glycol: Applications for Digestive Cancer Prevention

Abstract

Introduction: H. pylori transactivates the epidermal growth factor (EGFR) and induces extracellular-signal related kinase (ERK) phosphorylation in gastric epithelial cells which may be important in the pathway to gastric carcinogenesis. The green tea catechin epigallocatechin-3-gallate (EGCG) has been reported in some studies to have chemoprotective properties against development of gastric cancer. The aim of this study was to investigate if H. pyloriinduced ERK phosphorylation in A431 epithelial cells was inhibited by EGCG.Methods: H. pylori (NCTC 11637, cag PAI+) were co-cultured with A431 epithelial cells for 2.5 hrs. EGF (100 ng/ml) was used as a positive control. “In-Cell Western” (ICW) assay, which is a rapid quantitative method for determining the inhibitory effects of chemicals of interest on H. pylori epithelial cell signalling responses (REF Du Y et al., 2007), was used to examine the effects of EGCG on ERK1/2 phosphorylation (pERK) in A431 epithelial cells. EGCG (1-200 μM) was pre-incubated with A431 cells for 1 hr prior to the co-culture experiments. Results: EGF significantly (p<0.001, n=4) increased pERK in A431 cells compared to unstimulated controls. EGCG at concentrations greater than 50 μM caused a small but significant (p< 0.01) increase in pERK in A431 cells. EGCG dose-dependently significantly inhibited EGF (100 ng/ml)-induced pERK at a concentration of 10 μM and above (p<0.01, n=4). H. pylori strain NCTC 11637 significantly (p<0.01, n=4) increased pERK in A431 cells compared to unstimulated controls. EGCG dose-dependently inhibited pERK induced by H. pylori. EGCG at 100 μM significantly inhibited (p<0.05, n=4) H. pylori-induced pERK 2.5 hrs postculture. Conclusions: H. pylori-induced ERK phosphorylation in A431 epithelial cells was significantly inhibited by green tea catechin EGCG in a dose-dependent manner. The use of EGCG as dietary phytochemical for H. pylori-induced gastric cancer chemoprevention is plausible, at least in a specific group of patients with higher risk of gastric cancer development but failure for H. pylori eradication.