特异性抑制PI3K对胶质瘤生物学特性及EphA2/PI3K/MMPs通路的影响

Effect of PI3K specific inhibition on biological characteristics and EphA2/PI3K/MMPs pathway of glioma

目的通过磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K)特异性抑制剂LY294002处理高侵润性胶质瘤细胞U251,观察胶质瘤细胞增殖、迁移及侵袭变化,并检测受体型酪氨酸激酶(RTK)通路分子受体型酪氨酸激酶A2(erythropoietin-producing hepatocellular A2,EphA2)、PI3K、MMP-2表达,探讨胶质瘤信号通路作用机制。方法用不同浓度LY294002处理U251细胞,MTT法检测细胞增殖,Transwell法检测细胞迁移力及侵袭力,采用实时荧光定量PCR(real-time qPCR)检测细胞EphA2、PI3K、MMP-2 mRNA表达。结果LY294002呈剂量依赖性降低U251细胞的增殖、迁移、侵袭力,下调U251细胞PI3K、MMP-2表达,但对U251细胞EphA2表达无明显影响。结论LY294002剂量依赖性抑制人胶质瘤细胞增殖、迁移和侵袭,其机制可能与抑制PI3K/MMP-2通路有重要关系。

Objective To explore the mechanism of glioma signal pathway,the proliferation,migration,and invasion of glioma U251 cells were observed by the treatment with LY294002,a PI3K(phosphoinositide 3-kinase)specific inhibitor,and the expression of receptor tyrosine kinase(RTK)pathway molecules EphA2,PI3K,and MMP-2 were detected.Methods U251 cells were treated with different concentrations of LY294002.Cell proliferation was detected by MTT method,cell migration and invasion were detected by Transwell method,and the mRNA expressions of EphA2,PI3K,and MMP-2 were detected by real-time qPCR.Results LY294002 decreased the proliferation,migration,and invasion of U251 cells in a dose-dependent manner,decreased the expression of PI3K and MMP-2 in U251 cells,but had no significant effect on the expression of EphA2 in U251 cells.Conclusion LY294002 inhibited the proliferation,migration,and invasion of human glioma cells in a dosedependent manner.The mechanism may be related to the inhibition of PI3K/MMP-2 pathway.