碱性成纤维细胞生长因子经ERK信号通路抑制卵巢癌CAOV3细胞凋亡

Anti-apoptotic signal pathway of bFGF by ERK in ovarian cancer cell line CAOV3

目的:研究卵巢癌CAOV3细胞中碱性成纤维细胞生长因子(bFGF)经MEK/ERK1/2信号转导通路对CREB、Bcl-2表达以及对细胞凋亡的影响作用。方法:无血清饥饿诱导细胞凋亡。分为对照组、bFGF组、bFGF+PD98059组。Annexin-EGFP/PI荧光双染法检测细胞凋亡。Western印迹法检测ERK1/2、CREB以及Bcl-2蛋白表达。RT-PCR法检测Bcl-2的mRNA表达。结果:bFGF可抑制无血清饥饿诱导的细胞凋亡;时效依赖性地诱导ERK1/2活性增高、刺激CREB磷酸化、促进Bcl-2的mRNA及蛋白表达增加。bFGF作用CAOV3细胞15 min时ERK1/2活性达高峰;45 min时CREB磷酸化达峰值;Bcl-2的mREN表达高峰为6h,8h时蛋白表达最高。MEK1抑制剂PD98059可抑制bFGF的上述作用。结论:bFGF可能通过激活MEK/ERK1/2/CREB/Bcl-2信号转导途径抑制卵巢癌CAOV3细胞凋亡。

Objective： To investigate the effect of bFGF on the expression of CREB and Bcl-2 and to explore its anti-apoptotic mechanism by MEK/ERK1/2 signal transduction pathway in ovarian cancer cell line CAOV3. Methods： Cell apoptosis was induced by serum starvation. After bFGF treatment, the cell apoptosis, ERK1/2 activity, the expression of CREB and Bcl-2 were determined by FACScan flow cytometry, Western blotting and RT-PCR respectively. PD98059 （specific inhibitor of MEK1） was used to inhibit the effects of bFGF. Results： bFGF prevented the cell apoptosis. In a time-dependent way, bFGF induced ERK activity and the expression of phosphorylated CREB, and upregulated the mRNA and protein expression of Bcl-2. While PD98059 inhibited all the effects of bFGF mentioned above. Conclusion： bFGF may activate MEK/ERK1/2/CREB/Bcl-2 signal transduction pathway to prevent cell apoptosis in CAOV3 cell line, which may play an important role in growth and progress of ovarian cancer.