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目的:探讨Src信号通路在环孢素A(cyclosporin A,CsA)促进人滋养细胞侵袭中的作用。方法:应用Transwell侵袭实验观察CsA对人绒毛膜癌细胞株JEG-3侵袭能力的影响,应用Western blotting检测CsA作用于JEG-3细胞后Src的活化水平,并观察Src特异性抑制剂PP2对CsA作用后JEG-3细胞侵袭能力及E-钙粘蛋白表达水平的变化。结果:CsA可明显促进JEG-3细胞的侵袭(P<0.05),并可提高JEG-3细胞Src的活化水平(P<0.05),降低E-钙粘素蛋白的表达。PP2可明显抑制JEG-3细胞CsA诱导的Src活化(P<0.05),阻抑CsA对细胞侵袭的促进作用(P<0.05)和恢复CsA下调的E-钙粘蛋白表达水平(P<0.05)。结论:CsA可通过增强Src信号通路活化促进JEG-3细胞侵袭,并下调E-钙粘蛋白的表达,提示Src信号通路可能参与CsA对人滋养细胞生物学行为的良性调节作用。
Objective: To investigate the role of Src signaling pathway in promoting human trophoblast invasion by cyclosporin A (CsA). Methods: The invasion of human choriocarcinoma cell line JEG-3 was evaluated by Transwell invasion assay. The activation of Src was detected by Western blotting in JEG-3 cells. The effect of Src-specific inhibitor PP2 on CsA Involvement of JEG-3 cells in invasiveness and E-cadherin expression levels. Results: CsA could significantly promote the invasion of JEG-3 cells (P <0.05) and increase the activation of Src in JEG-3 cells (P <0.05) and decrease the expression of E-cadherin. PP2 could significantly inhibit the CsA-induced Src activation (P <0.05), inhibit CsA-induced cell invasion (P <0.05) and restore CsA-induced E-cadherin expression (P <0.05) . CONCLUSIONS: CsA can promote the invasion of JEG-3 cells and down-regulate the expression of E-cadherin by enhancing the activation of Src signaling pathway, suggesting that Src signaling pathway may be involved in the benign regulation of human trophoblast biological behavior by CsA.