替吉奥胶囊对胃癌细胞增殖、侵袭及凋亡的影响及机制研究

The effect of S-1 on proliferation,invasion and apoptosis of gastric cancer cell

目的探讨替吉奥胶囊对胃癌细胞增殖、侵袭及凋亡的影响及机制。方法 6.25μg/ml、12.5μg/ml、25μg/ml、50μg/ml、100μg/ml、200μg/ml的替吉奥处理人胃癌BGC823细胞,不加药物处理的作为空白对照组,48 h后,CCK8实验检测细胞增殖;Transwell小室检测细胞侵袭能力;流式细胞仪检测细胞凋亡;Western blot检测Cleaved caspase3、基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)、Notch1、Hes1蛋白表达。结果 6.25μg/ml、12.5μg/ml、25μg/ml、50μg/ml、100μg/ml、200μg/ml的替吉奥处理的细胞的抑制率均显著高于对照组,且具有浓度依赖性(P<0.01),选择115μg/ml的替吉奥作为后续实验的研究对象;与对照组比较,替吉奥组细胞抑制率显著升高,细胞侵袭数显著降低,细胞凋亡率显著升高,Cleaved caspase3蛋白表达显著上调,MMP-2、MMP-9、Notch1、Hes1蛋白表达显著下调(P<0.01)。结论替吉奥胶囊可降低胃癌细胞的增殖及侵袭能力,促进细胞的凋亡,其机制与抑制Notch1信号通路有关。

Objective To investigate the effect and mechanism of S - 1 on proliferation, invasion and apoptosis of gastric cancer cell. Methods 6. 25 μg/ml, 12. 5 μg/ml, 25 μg/ml, 50 μg/ml, 100 μg/ml, 200 μg/ml S - 1 treated human gastric cancer cell line BGC823 for 48 h, without drug treatment as control group ; cell proliferation was detected by CCK8 experiment ; the invasion ability of cell was detected by Tran-swell assay ; cell apoptosis was detected by flow cytometry ; the expression of Cleaved Caspase3 , MMP - 2 , MMP - 9 , Notchl , Hesl protein were detected by Western blot. Results Cell inhibition rate in 6.2 5μg/ml, 12.5μg/ml, 25 μg/ml, 50 μg/ml, 100 μg/ml, 200 μg/ml S - 1 treated group were significantly higher than that 0 μg/ml group, and in a concentration dependent manner （ P 〈0.01） , 115 μg/ml was selected as the research object in the follow - up experiment; compared with the control group, cell inhibition rate in S - 1 group was significantly increased, and cell invasion decreased significantly, the apoptosis rate was significantly increased, the expression of Cleaved Caspase3 protein was significantly up - regulated, the expression of MMP - 2, MMP - 9 , Notchl, Hesl protein was significantly lower （ P 〈0.01） . Conclusion S - 1 can reduce the proliferation and invasion of gastric cancer cells, promote cell apoptosis, and its mechanism is related to inhibition of Notchl signaling.