Objective: To explore the mechanism of prostaglandin E2(PGE2)affects the cell proliferation ability of human bile duct carcinoma cells CCLP1. Methods:CCLP1 cells were treated with PGE2,EP1-4 receptor agonist,AC agonist(Forskolin),PKA antagonist(H89),cAMP analogues(db-cAMP). The expression levels of SnoN mRNA and SnoN protein,and the cell proliferation ability were examined by RT-PCR,Western blot and WST methods in CCLP1 cells. Results:The expression of SnoN mRNA in CCLP1 cells increased by 22.5%(P < 0.01),while the level of snoN protein increased by 35.6%(P < 0.05)after treated with 10 μmol/L PGE2 for 24 h;The expression of SnoN protein in CCLP1 cells increased by 64.9%(P < 0.05)after treated with EP2 receptor agonist(10 μmol/L)for 24 h,and cell proliferation ability of CCLP1 increased by 26.5%;The levels of SnoN protein and CREB phosphorylation in CCLP1 cells increased by 25.1% and 71.3%(P < 0.05)respectively compared with the control group after treated with AC agonist Forskolin(10 μmol/L)for 24 h,and cell proliferation ability of CCLP1 increased by 4.4%(P < 0.05)after treated with 10 μmol/L Forskolin;The expression of SnoN in CCLP1 cells increased by 90.1%(P < 0.05)when treated with cAMP analogues db-cAMP(500 μmol/L)for 24 h,and decreased when treated with PKA antagonist H89(10 μmol/L)for 24 h,the levels of SnoN expression and CREB phosphorylation in CCLP1 cells treated with H89 decreased by 9.1% and 14.1%(p<0.05)compared with those treated with Forskolin.Cell prolifelation of CCLP1 decreased by 45.7%(p<0.05)after treated with 20 μmol/L H89.Conclusion:PGE2 might up-regulate the expression level of SnoN through EP2 receptor of CCLP1 cells which could be partly related to the cAMP-PKA-CREB signaling pathway,and promote the cell proliferation.