舒尼替尼对胃癌细胞BGC-823增殖的影响及机制

摘要

Objective:To explore the effects of sunitinib on the proliferation of BGC-823 in gastric cancer cells.Methods:BGC-823 gastric cancer cells were treated with different concentration sunitinib for 24 h,48 h,72 h and 96 h,and cell proliferation was determined by MTT method.The expression of Notch-1 and the level of apoptosis were detected by immunofluorescence staining method.The expressions of Notch-1,caspase-3 and caspase-9 protein were analyzed by Western blotting.Results:MTT results showed that the proliferation of BG-C-823 cells could be significantly inhibited by the time and dose dependent manners in the concentrations of 0.156 25-10 μmol/L.The results of immunofluorescence showed that the number of apoptosis increased in the treatment of BGC-823 cells with different concentrations.The results of Western blotting showed that the expression levels of the Notch-1 protein decreased with the different concentrations of sunitinib,and the expression level of caspase-3 was increased accordingly.Conclusion:By inhibiting the signal pathway activity of Notch-1,sunitinib inhibits the proliferation of BGC-823 cells and induces apoptosis.%目的:探索舒尼替尼对胃癌细胞BGC-823增殖的影响及机制.方法:不同浓度舒尼替尼处理BGC-823细胞24、48、72、96 h后,MTT法检测细胞增殖,得出药物的半数抑制浓度为0.592 8 μmol/L.筛选出比较接近半数致死量的3个药物浓度0.25、0.50、1.00 μmol/L作用细胞48 h后,细胞核染色检测细胞凋亡;免疫荧光染色法检测Notch-1的表达及细胞凋亡水平;蛋白质免疫印迹检测Notch-1、caspase-3、caspase-9蛋白表达水平.结果:MTT检测结果显示,舒尼替尼在浓度0.156 25～10μmol/L时可显著抑制BGC-823细胞增殖,且具有时间和剂量依赖性.细胞核染色结果显示,不同浓度的舒尼替尼处理BGC-823细胞48 h后随浓度的增加,细胞凋亡数量显著增多.蛋白质免疫印迹结果显示,不同浓度舒尼替尼作用48 h后,Notch-1蛋白的表达水平随浓度的增加而降低,caspase-3、caspase-9表达水平随浓度的增加而升高.结论:舒尼替尼通过抑制Notch-1的信号通路活性,进而抑制BGC-823细胞的增殖并诱导细胞凋亡.