Objective:To investigate the effect of Prostaglandin E2 on expression of E-Cadherin in HepG2 cells and its molecular mechanism. Methods:HepG2 cells were transfected with PCDNA3-COX-2; HepG2 cells were treated with Prostaglandin E2 and PI-3K inhibitor LY294002. Western blotting was employed to detect E-cadherin expression and the expression of p-Akt. E-cadherin mRNA levels were examined by reverse transcription-PCR(RT-PCR). Results:COX-2 plasmid transfected HepG2 cells show greatly decreased level of E-cadherin expression. when HepG2 cells were treated with different concentration of PGE2 for 24 h, the expression level of E-cadherin was decreased in a dose-dependent manner. When treated with 20 μmol/L PGE2 for 24 h,48 h and 72h, the level of E-cadherin mRNA was decreased in a time-dependent manner. By using PI-3K inhibitor LY294002, we found LY294002 could partially block the effect of PGE2 on E-cadherin expression. Akt phosphorylation level was remarkably increased in HepG2 cells when treated with PGE2, and reached the highest level at 15 minutes. Conclusion:Prostaglandin E2 can repress E-cadherin expression in HepG2 cells, which is probably related to the Akt signal transduction pathway.