前列腺素E2对人肝细胞癌HepG2细胞E-cadherin表达的影响及其分子机制
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国家自然科学基金资助(30470784,30871015)


Studies on E-cadherin expression inducement of Prostaglandin E2 in HepG2 cells and its molecular mechanism
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    摘要:

    目的:研究前列腺素E2(PGE2)对人肝细胞癌HepG2细胞E-cadherin表达的调节作用及其分子机制,探讨其与肝癌侵袭转移的关系,为肝癌的治疗提供新的研究思路-方法:COX-2瞬时转染人肝细胞癌HepG2细胞,Western blot实验检测其E-cadherin表达的变化;PGE2及PI-3K抑制剂LY294002处理人肝细胞癌HepG2细胞,应用Western blot和RT-PCR分别测定肝癌细胞内E-cadherin蛋白水平和mRNA水平的变化,并观察60 min内Akt磷酸化水平的变化-结果:COX-2过表达转染HepG2细胞后,E-cadherin的表达明显降低;5-10-20 μmol/L PGE2处理HepG2细胞24 h后,E-cadherin表达水平与对照组比较分别下降了22.31%-36.3%-47.83%(P < 0.05);20 μmol/L PGE2处理HepG2细胞 24-48-72 h,E-cadherin蛋白和mRNA的表达与对照组比均明显降低(P < 0.01)-PI-3K抑制剂LY294002能部分阻断PGE2对E-cadherin表达的调节作用;经PGE2处理的HepG2细胞Akt磷酸化水平显著升高,并且在15 min时达到最高-结论:PGE2可以抑制人肝细胞癌HepG2细胞中E-cadherin的表达,并很可能通过激活Akt信号转导通路而发挥作用-

    Abstract:

    Objective:To investigate the effect of Prostaglandin E2 on expression of E-Cadherin in HepG2 cells and its molecular mechanism. Methods:HepG2 cells were transfected with PCDNA3-COX-2; HepG2 cells were treated with Prostaglandin E2 and PI-3K inhibitor LY294002. Western blotting was employed to detect E-cadherin expression and the expression of p-Akt. E-cadherin mRNA levels were examined by reverse transcription-PCR(RT-PCR). Results:COX-2 plasmid transfected HepG2 cells show greatly decreased level of E-cadherin expression. when HepG2 cells were treated with different concentration of PGE2 for 24 h, the expression level of E-cadherin was decreased in a dose-dependent manner. When treated with 20 μmol/L PGE2 for 24 h,48 h and 72h, the level of E-cadherin mRNA was decreased in a time-dependent manner. By using PI-3K inhibitor LY294002, we found LY294002 could partially block the effect of PGE2 on E-cadherin expression. Akt phosphorylation level was remarkably increased in HepG2 cells when treated with PGE2, and reached the highest level at 15 minutes. Conclusion:Prostaglandin E2 can repress E-cadherin expression in HepG2 cells, which is probably related to the Akt signal transduction pathway.

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杨洪宝,张 海,冷 静.前列腺素E2对人肝细胞癌HepG2细胞E-cadherin表达的影响及其分子机制[J].南京医科大学学报(自然科学版),2009,29(3):281-285

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