Objective:To investigate the subtype of the EP3 and the related cell signal transduction pathway in human hepatocelluar carcinoma inorder to explore the molecular mechanism. Methods:The Huh7 cells were treated with different concertrations of Sulprostone for different times. The expression and splicesome type of EP3 was determined by RT-PCR. The cell viability was detected by WST-8. The level of intracellular cAMP concentration was measured by immunoassay Kit. and Western blott was employed to detect the expression of p-Akt and p-Erk. Results:The spliceosome of EP3 expressed in Huh7 is EP3(5). After the treatment of 10.0 μmol/L Sulprostone for 24 hours,the cells growth rate was increased 46.2%, and the level of cAMP in the cells was increased greatly. The remarkable increase of Akt phosphorylation and decrease of Erk phosphorylation could be observed by Western blott after the treatment of Sulprostone for 30 min. Conclusion:Our results suggested that the subtype of the EP3-EP3(5) mediated a great increasing of the intracellular concentration of cAMP in Huh7 cells,which is partly related to the Akt and Erk signaling pathway.