The Effect Of PGE₂ On Expression Of Survivin In Hepatocellular Carcinoma

Background:Cyclooxyenase-2 (COX-2) and its product PGE₂ play an important role in tumor genesis, development and metastasis. Many researches indicate that PGE₂ can promote tumor growth by binding to its receptors and activating signaling pathways which control cell proliferation, migration, apoptosis, and/or angiogenesis. However, the biological role and molecular mechanism of PGE₂ in the tumorigenesis have not been established.Survivin is a new member of inhibitors of apoptosis proteins (IAP). It was expressed mainly in developing embryonic tissue also frequently in malignant tumors of human but not in differentiated tissue (except thymus). Its biological effects are inhibiting apoptosis, regulating cell propagate and inducing angiogenesis. The tissue-specific expression of survivin protein makes it to be a new target of tumor diagosis and treatment. Many studies showed that both PGE₂ and Survivin played an important role in the process in the genesis, development and angiopoiesis of tumor. Wether there is a correlation between PGE₂ and Survivin or wether there is any possibility of PGE₂ and Survivin serving in the diagnosis and treatment of tumor as joint targets have not been reported.In this article, to investigate the effect and mechanism of PGE₂ on expression of Survivin, we studied the effects of PGE₂, EP receptor agonist, EP receptor inhibitor, LY294002 on HCC cell in vitro.Objective:To investigate the effect and mechanism. of PGE₂ on expression of Survivin in HuH7 cell line. To supply experimental evidence for gene diagnosis and treatment of HCC.Methods:1. Cell culture: HCC cell line HuH7 was cultured in vitro as routine.2. HuH7 cells were treated with PGE₂, EP receptor agonist, EP receptor inhibitor, and LY294002.3. Western blotting was employed to detect the expression of Survivin in HuH7 cells.Results:1. The expression of Survivin in HuH7 cells was increased by 63.59% (P <0.01)vs control after treated with exogenous PGE₂ for 8h.2. The expression of Survivin in HuH7 cells were increased by 114.76%(P<0.01),76.68%(P<0.01) and 70.01% (P<0.01)vs control after treated with exogenous EP1, EP3, EP4 receptor agonist for 8h respectively, but had no change after treated with exogenous EP2 receptor agonist(P>0.05).3. The expression of Survivin in HuH7 cells were decreased by 32.95%(P<0.01)and 28.36%(P<0.05)vs PGE₂ after treated with exogenous EP1, EP4 receptor inhibitor for 8h respectively, but had no change after treated with exogenous EP2 receptor inhibitor(P>0.05).4. The expression of Survivin in HuH7 cells was decreased by 28.05%(P<0.01) vs PGE₂ after treated with exogenous LY294002 for 8h. Conclusion:Our findings suggested that PGE₂ might up-regulate the expression of Survivin mainly through EP1, EP3 and EP4 receptors, which could be partly related to the PI3K/AKT Signal Conduction Pathway.