新型小分子靶向药物F90对人恶性胶质瘤细胞系SHG-44生长抑制作用

The study on antitumor activity of a novel small molecular target drug F90,in human malignant glioma cell line SHG-44

目的探讨新型小分子靶向药物F90在体外对人恶性胶质瘤细胞系SHG-44的生长抑制作用。方法采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐[3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT]方法,集落生成试验探讨F90对SHG-44细胞的生长抑制作用,采用蛋白免疫印迹(Immunoblotting,West-ernblot)方法检测F90对表皮生长因子受体(epidermal growth factor receptor,EGFR)信号传导通路及凋亡相关蛋白的影响。结果 F90抑制SHG-44细胞的生长,并且呈一定的剂量相关性。MTT试验及集落生成试验的半数有效抑制浓度(50% inhibitory concentration,IC50)分别为(5.08±1.21)μmol/L和(0.14±0.03)μmol/L。F90抑制EGFR及其下游通路信号蛋白的磷酸化,上调P53蛋白的表达,并下调BCL-2蛋白的表达。结论 F90可能通过干扰EG-FR通路,体外抑制胶质瘤细胞株SHG-44的生长。

Objective To investigate the antitumor activity of F90,a novel small molecular target drug,in human malignant glioma cell line SHG-44.Methods Antitumor activity of F90 was detected using 3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay and colony formation test.Effects of F90 on epidermal growth factor receptor （EGFR） pathway and apopotosis relating proteins were investigated using western blot assay.Results F90 inhibited SHG-44 cell growth in a dose-dependent manner as evidenced by MTT assay and colony formation test in vitro.The 50% inhibitory concentrations （IC50 s） of F90 on cell growth and colony-forming were 5.08±1.21 μmol/L and 0.14±0.03 μmol/L,respectively.F90 inhibited phosphorylation of epidermal growth factor receptor （EGFR） and its downstream signaling protein,up-regulated P53 and down-regulated BCL-2.Conclusions Interference of EGFR pathway may be the mecanism of antitwmor actiuity of F90 on SHG cau in vitro.