STAT3信号通路抑制剂AG490协同TCF21促进卵巢癌细胞凋亡的实验研究

Experimental study on STAT3 signaling pathway inhibitor AG490 combined with TCF21 to promote apoptosis of ovarian cancer cells

目的:探讨信号转导与转录因子3(STAT3)信号通路抑制剂AG490对过表达转录因子21(TCF21)的卵巢癌细胞凋亡的影响。方法:卵巢癌细胞ES-2转染TCF21过表达载体,Western blot检测转染后细胞中TCF21表达情况。ES-2细胞分为对照组(未转染且正常培养)、过表达组(转染TCF21过表达载体)、抑制剂组(未转染的细胞经过STAT3信号通路抑制剂处理)、联合组(STAT3信号通路抑制剂处理过表达TCF21的细胞)。噻唑蓝(MTT)检测细胞增殖,流式细胞术检测细胞凋亡,Western blot检测STAT3、磷酸化STAT3(p-STAT3)、剪切后的Caspase-3(Cleaved Caspase-3)蛋白表达。结果:转染TCF21过表达载体的ES-2细胞中TCF21表达水平升高明显高于对照组(P<0.05)。过表达组和抑制剂组细胞增殖率和p-STAT3/STAT3水平明显低于对照组且明显高于联合组(P<0.05)。过表达组和抑制剂组细胞凋亡率和Cleaved Caspase-3水平明显高于对照组且明显低于联合组(P<0.05)。结论:STAT3信号通路抑制剂能够协同TCF21促进卵巢癌细胞凋亡并抑制卵巢癌细胞增殖。

Objective:To investigate the effect of inhibitor of STAT3 signaling pathway AG490 on apoptosis of ovarian cancer cells overexpressing TCF21.Methods:Ovarian cancer cell ES-2 transfected TCF21 overexpression vector.The expression of TCF21 in transfected cells was detected by Western blot.ES-2 cells were divided into control group(non-transfected and normal culture)and overexpression group(transfected with TCF21 expression vector),inhibitor group(non-transfected cells cultured with STAT3 signaling pathway inhibitor)and combined group(STAT3 signaling pathway inhibitor treated cells overexpressing TCF21).Cell proliferation was detected by MTT.Apoptosis was detected by flow cytometry.The expression of STAT3,p-STAT3,Cleaved Caspase-3 protein were detected by Western blot.Results:The expression level of TCF21 in ES-2 cells transfected with TCF21 overexpression vector increased more than control group(P<0.05).Cell proliferation rate and p-STAT3/STAT3 levels in overexpression group and inhibitor group were significantly lower than the control group,and them in the combined group were significantly lower than overexpression group and inhibitor group(P<0.05).The apoptosis rate and the level of Cleaved Caspase-3 in the overexpression group and the inhibitor group were significantly higher than those in the control group,and significantly lower than that in the combined group(P<0.05).Conclusion:STAT3 signaling pathway inhibitors can promote apoptosis and inhibit proliferation of ovarian cancer cells in combination with TCF21.