丙泊酚对人胶质瘤U251细胞株增殖、凋亡、侵袭和转移能力的调节作用

The regulatory effects of propofol on cell proliferation, apoptosis, invasion and migration of human glioma cell line U251

目的探究丙泊酚对人胶质瘤U251细胞增殖、凋亡、侵袭和转移能力的作用和机制。方法将细胞随机分为U251组、Propofol(1mM)组、Propofol(2mM)组和Propofol(5mM)组。除U251组外,其余组用相应浓度的丙泊酚处理,CCK8检测细胞增殖,流式检测细胞凋亡,Transwell检测细胞侵袭能力,划痕实验检测细胞迁移能力,Westernblot检测Ki67、Caspase-3、血管内皮生长因子(Vascularendothelialgrowthfactor,VEGF)、磷脂酰肌醇-3-羟激酶(Phosphoinositide3-kinase,PI3K)、Akt、p-PI3K和p-Akt的表达。结果与U251组比较,Propofol(1,2,5mM)组细胞增殖速度明显降低,细胞凋亡率显著升高;同时,Propofol(1,2,5mM)组侵袭细胞数与U251组比较明显减少,Propofol(2,5mM)组划痕闭合率明显低于U251组;此外,丙泊酚还能显著抑制细胞增殖和迁移相关蛋白Ki67和VEGF表达,诱导细胞凋亡相关蛋白Caspase-3表达;丙泊酚能明显降低p-PI3K/PI3K和p-Akt/Akt的比值。结论丙泊酚能降低胶质瘤U251细胞的增殖、侵袭和转移能力,抑制U251细胞凋亡,作用机制可能与抑制PI3K/Akt信号通路激活有关。

Objective To investigate the effects and mechanism of propofol on cell proliferation,apoptosis, invasion and migration of human glioma cell line U251. Methods Cells were divided into Propofol(1 M), Propofol(2 M) and Propofol(5 M) group and treated with propofol bisides U251 group. Cell proliferation was determined by CCK8 assay, flow cytometry was performed for cell apoptosis. The invasion and migration abilities of U251 cell were determined by Transwell and wound healing assays. The expressions of Ki67, Caspase-3, vascular endothelial growth factor(VEGF), phosphoinositide 3-kinase(PI3K), Akt, pPI3K and p-Akt were measured by western blot. Results Compared with U251 group, the cell growth rate was decreased and cell apoptosis rate was increased in Propofol(1, 2, 5 M) groups. Meanwhile, the invasion cells in the propofol(1, 2, 5 M) groups were decreased compared with the U251 group, and wound closure rate was also down-regulated in the propofol(2, 5 M) groups. In addition, propofol inhibited the expressions of Ki67 and VEGF(proliferation-and migration-related proteins) and induced expression of apoptosis-related protein Caspase-3. Propofol also decreased the ratio of p-PI3K/PI3K and p-Akt/Akt significantly.Conclusions Propofol reduces the abilities of cell proliferation, invasion and migration of glioma cell line U251 and induces cell apoptosis, the mechanism of which may be related to inhibition of the activation of PI3K/Akt signaling pathway.