PGE2对HuH7细胞Survivin表达影响的研究

The effect of PGE_2 on the expression of Survivin in hepatocellular carcinoma

目的:研究前列腺素E2(PGE2)对人肝癌细胞HuH7Survivin表达的影响及其与PI3K/AKT信号转导通路的相关性。方法:用PGE2、EP受体激动剂、EP受体抑制剂、PI3K抑制剂(LY294002)处理HuH7细胞,用Westernblot检测Survivin蛋白表达。结果:5μmol/LPGE2处理HuH7细胞8h后,Survivin的表达水平与对照组相比上升了63.59%(P<0.01);5μmol/LEP1、5μmol/LEP3、5μmol/LEP4受体激动剂分别处理HuH7细胞8h后,Survivin的表达水平与对照组相比分别上升了114.76%(P<0.01),76.68%(P<0.01),70.01%(P<0.01),而5μmol/LEP2受体激动剂处理HuH7细胞8h后,Survivin的表达水平与对照组相比无明显改变(P>0.05);10μmol/LEP1,10μmol/LEP4受体抑制剂分别处理HuH7细胞8h后,Survivin的表达水平与PGE2组相比分别下降了32.95%(P<0.01),28.36%(P<0.05),而10μmol/LEP2受体抑制剂处理HuH7细胞8h后,Survivin的表达水平与PGE2组相比无明显改变(P>0.05);10μmol/LPI3K抑制剂(LY294002)处理HuH7细胞8h后,Survivin的表达水平与PGE2组相比下降了28.05%(P<0.01)。结论:PGE2可能通过EP1、EP3、EP4这3种受体影响HuH7细胞中Survivin的表达,且这种调节作用可能与PI3K/Akt信号转导通路有关。

Objective：To investigate the effect of PGE2 on the expression of Survivin in HuH7 cell line and its correlation with PI3K/AKT signal conduction pathway. Methods： HuH7 cells were treated with PGE2, Celecoxib （EP receptor agonist）, LY294002（EP receptor inhibitor）. Western blotting was employed to detect the expression of Survivin in HuH7 cells. Results：The expression of Survivin in HuH7 cells were increased by 63.59%, 114.76%,76.68% and 70.01%（P 〈 0.01）after treatment of PGE2 （5 μmol/L） and EP1, EP3,EP4 receptor agonist（5 μmol/L）for 8 h,and decreased by 32.95%（P 〈 0.01）and 28.36%（P 〈 0.05） after treatment of EP1 and EP4 receptor inhibitor （10 μmol/L）for 8 h respectively,but have no change after treatment of EP2 receptor agonist （5 μmol/L） and EP2 receptor inhibitor （5 μ mol/L） （P 〉 0.05）. After the treatment of LY294002 （10 μmol/L） for 8 h,the expression of Survivin in HuH7 cells were decreased by 28.05% （P 〈 0.01） vs that treated with PGE2 . Conclusion：Our findings suggested that PGE2 might up-regulate the expression of Survivin through EP1,EP3 and EP4 receptors,which could be partly related to the PI3K/AKT signal conduction pathway.