Objective:To explore VEGF expression induced by PGE2 in human hepatocellular carcinoma cells HuH7 and the possible mechanisms of signal transduction pathways. Methods:HuH7 cells were treated with PGE2,EP1-4 receptor agonist,SQ22536+PGE2,H89+PGE2. VEGF mRNA and protein expression were examined by Real-time PCR,Western blot and ELISA in HuH7 cells. Results:The expression of VEGF mRNA in HuH7 cells were increased by 264%(P < 0.01),and the expression of VEGF in culture supernatant of HuH7 cells were increased by 24%(P < 0.01)after treated with PGE2(10 μmol/L) for 24 h. The expression of VEGF in cytoplasm of HuH7 cells were increased by 13.6%,25.7%,39.6% (P < 0.01)after treated with PGE2 (10 μmol/L) for 6 h,12 h,24 h respectively. The expression of VEGF in cytoplasm and culture supernatant of HuH7 cells were increased by 32.3% and 20.1%(P < 0.01)after treated with EP2 receptor agonist(10 μmol/L) for 24 h respectively,but have no changes after treated with EP1,EP3,EP4(10 μmol/L) receptor agonist. After the treatment of H89 (30 μmol/L) and SQ22536(500 μmol/L) for 24 h,the expression of VEGF in cytoplasm of HuH7 cells was decreased by 91.6% and 89.6%,and the expression of VEGF in culture supernatant of HuH7 cells was decreased by 98.3% and 91.9%,respectively,vs PGE2(P < 0.01). Conclusion:It is suggested that PGE2 might up-regulate the expression of VEGF through EP2 receptor of HuH7 cells,which could be partly related to the cAMP-PKA signal conduction pathway.