Jagged1-STAT 3信号轴对卵巢癌细胞A 2780迁移能力的影响

目的探讨Jagged1调控STAT 3对卵巢癌A 2780细胞迁移能力的影响。方法 Notch信号特异性阻断剂γ-分泌酶抑制剂(N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester,DAPT)以浓度梯度的方式(0μM、2.5μM、5μM、10μM、20μM和40μM)处理卵巢癌A 2780细胞,通过CCK-8和平板克隆实验分析细胞增殖能力,Transwell迁移实验和体外划痕实验检测A 2780细胞迁移能力,Western blot检测Jagged1、STAT 3和p-STAT 3的蛋白表达。结果实验组细胞的平板克隆形成能力均低于对照组细胞,且随浓度升高呈逐级递减趋势,且10μM DAPT处理后的细胞下降最明显(P0.05)。实验组的迁移能力明显低于对照组,且呈时间梯度和浓度梯度的方式降低(P0.05)。卵巢癌A 2780细胞中Jagged1下调p-STAT 3表达以浓度和时间依赖的方式,DAPT浓度大于10μM有明显抑制作用(P0.05);STAT 3蛋白表达的作用变化无明显差异(P0.05)。结论抑制Jagged1可下调STAT 3导致卵巢癌A 2780细胞活力、增殖和迁移能力降低,Jagged1可能成为卵巢癌治疗的潜在新靶点。

Effect of Jagged1-STAT 3 signal axis on migration ability of ovarian cancer cell A 2780

Objective To investigate the effect of Jagged1 regulated STAT 3 on the migration ability of ovarian cancer A 2780 cells.Methods Ovarian cancer A2780 cells were treated with γ-secretase inhibitor(N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester, DAPT)in dose-dependent manner(0 μM,2.5 μM,5 μM,10 μM,20 μM and 40 μM).The ability of proliferation in the 6 groups of A2780 cells was detected by CCK-8 and plate cloning assay.The ability of migration of A2780s in vitro was examed through wound healing and transwell migration assay.The protein expression of Jagged1 and STAT3/p-STAT3 were analyzed through western blot.Results Compared with the control group,the growth rate of A2780s decreased with the increase of concentration of DAPT.The cloning formation rate of A2780s gradually increased and A2780s treated by the concentration of 10 μM DAPT decreased most obviously.The ability of migration of experimental group decreased with the increase of concentration, and was significantly lower than that in the control group(P<0.05).The protein expression of Jagged1 and p-STAT3 through western blot in A2780s decreased in a dose-dependent manner(P<0.05);the protein expression of STAT3 did not change significantly(P>0.05).Conclusion STAT3 is an important downstream target gene of Jagged1, which can affect the ability of migration in ovarian cancer A2780s by regulating the expression of STAT3.