The aim of this study was to assess whether (－)-epigallocatechin-3-gallate (EGCG) regulates autophagy during cerulein-induced acute pancreatitis (AP). Pancreatitis was induced in 10~12 week-old female Swiss Webster mice (n=3/group) pretreated with EGCG (2.5 mM/kg/day) by intraperitoneal injection for 4 days before injecting cerulein (50 Ռg/kg) i.p. for 9 h. The pancreases were harvested 1 h after the last injection. Weights of pancreases and amylase levels in serum were used to assess the development of AP. The pancreatic levels of phospho-ERK (pERK), beclin1 and cleaved LC3-II, were assessed by Western blotting. Pancreas wet weight, serum amylase and pERK levels were increased by cerulein, as compared to those of EGCG treated group. Cerulein also increased levels of beclin1 and cleaved LC3-II, as compared to those of EGCG treated group. Amylase, pERK and autophagy proteins returned to basal levels by EGCG treatment. In conclusion, treatment of EGCG regulated autophagy during induction of AP through the MEK/ERK pathway. Targeted modulation of the MEK/ERK pathway by EGCG may provide novel therapeutic strategies for reducing the severity of AP. (Cancer Prev Res 17, 0-238, 2012)

Keywords: Pancreatitis, EGCG, Cerulein, Autophagy, MAPK, Beclin-1, LC-II