亚硒酸钠与白藜芦醇联合应用对肺癌细胞的协同效应分析

Synergistic Effect of Sodium Selenite and Resveratrol on Lung Cancer Cell Line

目的:观察亚硒酸钠与白藜芦醇单独及联合应用对肺癌细胞的影响,并通过细胞周期探讨其作用机理。方法:用四甲基偶氮唑盐法检测亚硒酸钠和白藜芦醇单独及联合应用对细胞增殖和存活的影响;用流式细胞术测定细胞的凋亡率及细胞周期。结果:亚硒酸钠和白藜芦醇对肺癌细胞A549均有拮抗作用,且随浓度的增加,拮抗效果越显著,当亚硒酸钠浓度大于等于5μmol/L时,拮抗效果极显著(P<0.01);当白藜芦醇浓度大于等于65μmol/L时,拮抗效果极显著(P<0.01)。亚硒酸钠对A549细胞的半致死率(lethal dose of 50%,LD_(50))为4.759μmol/L,白藜芦醇对A549细胞的LD_(50)为45.24μmol/L。然而亚硒酸钠和白藜芦醇联合用药作用于A549细胞的拮抗效果优于单独用药,且低剂量的亚硒酸钠和白藜芦醇联合就能发挥出高剂量亚硒酸钠对A549细胞的拮抗作用效果,有效地降低了亚硒酸钠对细胞的毒副作用。另外,亚硒酸钠联合白藜芦醇作用可以阻滞A549细胞G0/G1期,最终导致细胞凋亡。

Objective: To investigate the effect of sodium selenite,resveratrol and their combination on the proliferation and apoptosis of lung cancer cell line A549 cells and to explore the underlying mechanisms.Methods: Methyl thiazolyl tetrazolium(MTT) method was used to assess the individual and combined effects of sodium selenite and resveratrol on proliferation and survival of A549 cells.The cell apoptosis rate and cell cycle were determined by flow cytometry.Results indicated that sodium selenite and resveratrol had an antagonistic effect on A549 cells in a concentration-dependent manner,and the effect was very significant at a concentration ≥ 5 μmol/L for sodium selenite and ≥ 65 μmol/L for resveratrol(P < 0.01).The median lethal doses of(LD_(50)) of sodium selenite and resveratrol for A549 cells were 4.759 and 45.24 μmol/L,respectively.However,when sodium selenite and resveratrol were used in combination,a synergistic effect was observed.The combination of low-dose sodium selenite and resveratrol inhibited A549 cells as effectively as high-dose sodium selenite,greatly reducing the cytotoxicity of high-dose sodium selenite.In addition,the combination of sodium selenite and resveratrol arrested the cell cycle at the G0/G1 phase and ultimately led to cell apoptosis.