F90对胶质母细胞瘤细胞的作用及机制研究

Effect and antitumor mechanism of F90 on glioblastoma cells

目的探讨表皮生长因子受体(EGFR)抑制剂F90对胶质母细胞瘤(GBM)细胞的抑制作用及其机制。方法采用MTT法检测F90对GBM细胞的抑制作用,流式细胞术检测细胞凋亡和免疫印迹法(Western Blot)检测蛋白表达。结果F90能明显抑制U251和SHG-44细胞的生长,半数抑制浓度(IC50)分别为(5.8±1.3)和(5.1±1.2)μmol/L,且呈一定的剂量相关性。F90可以诱导U251细胞的凋亡,抑制U251细胞EGFR的磷酸化及其丝裂原活化的蛋白激酶(MAPK)通路下游信号的活化,下调Bcl-2蛋白的表达,上调P53蛋白的表达。结论F90能有效抑制某些GBM细胞在体外的生长,与Iressa作用强度相当,有可能成为一种新的治疗GBM的药物。

Objective To investigate the antitumor effects and antitumor mechanism of F90, a kind of inhibitor of epidermal growth factor receptor （EGFR） on glioblastoma （GBM） cells. Methods Antitumor activity of F90 was detected by MTT assay. The antitumor mechanism was investigated by flow cytometry and Western Blot assay. -Results U251 and SHG-44 cells were inhibited by F90 in a dose-dependent manner in vitro. The 50% inhibitory concentration （IC50） of them was 5.8±1.3 and 5.1±1.2 μmol/L, respectively. F90 inhibited phosphorylation of EGFR and downstream signaling proteins of mitogen-activated protein kinase （MAPK） pathway, up-regulated P53 protein and downregulated Bcl-2 protein, induced cell apoptosis confirmed by flow cytometry. Condusion F90 is effective for growth inhibition of some GBM cells in vitro and has a similar effect to Iressa, therefore may be a novel potent agent for GBM.