丙泊酚对滋养细胞增殖、侵袭的影响及相关机制研究

Effects of propofol on proliferation and invasion of trophoblasts and its action mechanism

目的探讨丙泊酚对滋养细胞JEG-3增殖、侵袭的影响并探讨可能机制。方法试验分为对照组、低剂量丙泊酚组(1μg/ml)、中剂量丙泊酚组(4μg/ml)、高剂量丙泊酚组(7μg/ml),通过CCK-8法检测丙泊酚对滋养细胞JEG-3增殖的影响,通过Transwell小室法检测丙泊酚对滋养细胞JEG-3增殖、侵袭的影响,通过免疫印迹法(WB)检测增殖侵袭相关蛋白及PI3K/Akt通路相关蛋白表达情况,在高剂量丙泊酚基础上添加PI3K/Akt信号通路特异性抑制剂LY294002检测其对细胞增殖、侵袭迁移及相关蛋白表达影响。结果与对照组比较,同一时间内丙泊酚1μg/ml组、丙泊酚4μg/ml组、丙泊酚7μg/ml组增殖抑制率依次升高,差异有统计学意义(P<0.05);与对照组比较,丙泊酚1μg/ml组、丙泊酚4μg/ml组、丙泊酚7μg/ml组侵袭、迁移细胞数依次下降,差异有统计学意义(P<0.05);与对照组比较,丙泊酚1μg/ml组、丙泊酚4μg/ml组、丙泊酚7μg/ml组增殖相关蛋白PCNA以及侵袭迁移相关蛋白MMP-2、MMP-9蛋白、p-PI3K/PI3K、p-Akt/Akt表达依次降低,差异有统计学意义(P<0.05);与丙泊酚7μg/ml组比较,丙泊酚+抑制剂组细胞增殖抑制率显著增加,差异有统计学意义(P<0.05),侵袭、迁移细胞数显著降低,差异有统计学意义(P<0.05),PCNA、MMP-2、MMP-9、p-PI3K/PI3K、p-Akt/Akt蛋白表达显著降低,差异有统计学意义(P<0.05)。结论丙泊酚可能通过抑制PI3K/Akt信号通路活化,抑制滋养细胞JEG-3增殖、侵袭迁移。

Objective To investigate the effects of propofol on the proliferation and invasion of trophoblast-EG-3,and to explore the possible action mechanism.Methods The experiment was divided into control group,low dose propofol group(1μg/ml),medium dose propofol group(4μg/ml)and high dose propofol group(7μg/ml).The effects of propofol on the proliferation of trophoblast-JEG-3 were detected by CCK-8 assay,and the effects of propofol on the proliferation and invasion of trophoblast-JEG-3 were detected by Transwell chamber assay.Moreover the expression levels of proliferation and invasion related proteins and PI3K/Akt pathway related proteins were detected by Western Blot(WB),and the effects of PI3K/Akt signaling pathway specific inhibitor LY294002 on cell proliferation,invasion,migration and related protein expression were detected by adding it on the basis of high dose propofol.Results As compared with those in control group,the inhibition rates of propofol 1μg/ml group,propofol 4μg/ml group and propofol 7μg/ml group were significantly increased in turn at the same time(P<0.05).As compared with those in control group,the numbers of invasive and migrating cells were significantly decreased in propofol 1μg/ml group,propofol 4μg/ml group and propofol 7μg/ml group(P<0.05).As compared with those in control group,the expression levels of proliferation-related protein PCNA and invasion and migration related proteins MMP-2,MMP-9,p-PI3K/PI3K and p-Akt/Akt in propofol 1μg/ml group,propofol 4μg/ml group and propofol 7μg/ml group were significantly decreased in turn(P<0.05).As compared with that in propofol 7μg/ml group,the inhibition rate of cell proliferation propofol+inhibitor group was significantly increased(P<0.05),and the numbers of invasive and migrating cells were significantly decreased(P<0.05),moreover,the expression levels of PCNA,MMP-2,MMP-9,p-PI3K/PI3K,p-Akt/Akt protein were significantly decreased(P<0.05).Conclusion Propofol may inhibit the proliferation,invasion and migration of trophoblast-JEG-3 by inhibiting the activation of PI3K/Akt signaling pathway.