维生素K_2与苯那普利诱导胃癌细胞凋亡及抑制血管生成的体外实验研究

Combined treatment of vitamin K_2 and benazepril induces apoptosis and inhibits angiogenesis on gastric cancer in vitro experiments

目的:通过体外细胞培养观察维生素K2联合苯那普利对人胃癌SGC-7901细胞的影响,以探讨两者对胃癌细胞的影响及有无协同作用。方法:通过人胃癌SGC-7901细胞培养,将处于对数生长期的SGC-7901细胞分成5组:药物组(维生素K2组、苯那普利组、联合组)、阴性对照组和空白对照组,阴性对照组不加药,空白对照组不加细胞。加入不同终浓度的药物(维生素K2:5、10、20、40、80μmol/L)或(苯那普利:0.625、1.25、2.5、5、10μg/mL)或(维生素K2+苯那普利)。分别培养24、48和72 h。利用MTT实验检测细胞生长抑制率,流式细胞仪Annexin V/PI双染法及梯状DNA电泳检测细胞凋亡情况,RT-PCR测定血管内皮生长因子(VEGF)表达。结果:药物组能抑制胃癌SGC-7901细胞的增殖,且具有明显的剂量-效应关系,在抑制细胞增殖、诱导细胞凋亡及抑制VEGF表达方面,联合组较单独药物组作用更强。结论:维生素K2与苯那普利联合有协同作用,能通过诱导细胞凋亡、抑制VEGF的表达抑制胃癌细胞增殖。

AIM：To investigate the effect of vitamin K2 combined with benazepril on human gastric carcinoma SGC-7901 cells in vitro. METHODS： SGC-7901 cells at logarithmic growth phase were obtained and were divided into 5 groups： negative control group,blank control group,vitamin K2 therapy group,benazepril therapy group and combination therapy group（vitamin K2＋benazepril）.SGC-7901 cells were cultured with drugs of different concentrations（vitamin K2： 5,10,20,40,80 μmol/L）or benazepril（benazepril： 0.625,1.25,2.5,5,10 μg/mL） or vitamin K2＋benazepril for 24,48 and 72 h in drugs group.Cells cultured without drugs were served as negative control and blank control group without cells.The inhibition rates of SGC-7901 cells were detected by MTT assay,apoptosis rate of SGC-7901 cells was determined by Annexin V/PI double staining flow cytometry and DNA ladder,cell cycles of SGC-7901 cells were analysed by flow cytometry and VEGF expression of SGC-7901 cells were detected with RT-PCR.RESULTS：Vitamin K2 or benazepril had significant inhibitory effect on SGC-7901 cells growth,but combination group was more effective than the drug group alone on SGC-7901 cells proliferation,apoptosis and VEGF expression.CONCLUSION： Vitamin K2 combined with benazepril have obvious coordination therapeutic effect.The proliferation of SGC-7901 cells could be inhibited by inducing apoptosis and inhibiting VEGF expression.