ERα通过MTA3调控EMT影响HCC细胞凋亡的研究

Role of ERα in Governing EMT via MTA3 and Its Correlation with Apoptosis in HCC Cells

目的在肝细胞性肝癌(HCC)细胞中,探讨雌激素受体α(ERα)通过肿瘤转移相关基因3(MTA3)调控HCC细胞上皮-间质转换(EMT)对HCC细胞凋亡的影响。方法使用雌二醇、氟维司琼干预HCC细胞中ERα的表达,采用real-time PCR测定信号通路中关键因子MTA3、EMT关键调节因子Snail、E-cadherin,及凋亡相关因子BAX在处理前后mRNA水平的改变,探讨ERα、MTA3改变与HCC细胞EMT和凋亡改变的关系。结果 ERα→MTA3→Snail→E-cadherin信号通路各相关因子在部分HCC细胞(HepG2)中表达。雌二醇处理ERα高表达的HepG2细胞后,Snail表达下降,E-cadherin表达上升,EMT被抑制;BAX表达上升,HCC细胞凋亡增加。氟维司琼处理后,Snail表达上升,E-cadherin表达下降,EMT被激活;BAX表达下降,HCC细胞凋亡被抑制,而在ERα低表达的SMMC-7721细胞中,则没有明显差异。结论 ERα高表达的HCC细胞中,ERα→MTA3→Snail→E-cadherin信号通路存在并调节EMT。雌二醇可以激活ERα表达,抑制EMT进而抑制细胞凋亡,而氟维司琼则可以通过抑制ERα,激活EMT。

Objective To investigate the role of ERα and MTA3 in EMT via ERα→MTA3→Snail→E - cadherin signaling pathway and the correlation with cell apoptosis in HCC cells. Methods The HCC cells were treated with different concentrations of estradiol and fulvestrant for 48 hours. Expression of MTA3 ,Snail and E - cadherin mRNA, apoptosis protein BAX mRNA were detected by real time PCR. Results The molecular involved in ERα→MTA3→Snail→E - cadherin signaling pathway were existed in some of the HCC cells such as HepG2. In ERct positive HCC cell HepG2, more expression of MTA3, less expression of Snail and more expression of E - cadher- in was detected in HepG2 cells after the treatment of estradiol, and these changes were correlated with a higher expression of BAX. The opposite changes were observed in HepG2 cells after treated with fulvestrant. However, in ERα negative HCC cell SMMC - 7721, no change of these factors could be detected. Conclusion ERα→MTA3→Snail→E - cadherin signaling pathway was existed in some of the HCC cells and governed EMT. Estradiol could suppress EMT via this signaling pathway in ERα positive HCC cell HepG2, while fulves- trant had the opposite function.