MLN4924促进人肺腺癌细胞株A549凋亡的机制研究

In vitro Study on the Mechanism of MLN4924-induced Apoptosis in Human Lung Cancer Cell Line A549

目的:观察MLN4924对人肺腺癌A549细胞增殖、凋亡的影响,探讨MLN4924促进凋亡的作用机制。方法:不同浓度的MLN4924作用细胞不同时间后,采用CCK-8检测细胞增殖抑制率;Hoechst33342荧光染色、流式细胞仪检测细胞凋亡率及细胞周期;Western blot检测凋亡相关蛋白Caspase-3、NF-κB p65及CDT1相对表达量。结果:MLN4924能够明显抑制A549细胞的增殖,并且具有浓度和时间依赖性。流式细胞仪检测结果显示药物作用后,细胞被阻滞在S期。Western blot结果显示药物作用后细胞内Caspase-3、CDT1蛋白的表达量增加,而NF-κB p65的表达量减少。结论:MLN4924能够明显抑制A549细胞增殖、促进细胞凋亡,其相关机制为MLN4924可阻滞细胞于S期,增加Caspase-3蛋白表达,抑制NF-κB通路的激活。

Objective： To study the effect of MLN4924 on the proliferation and apoptosis of lung epithelial carcinoma A549 cells. Methods： A549 cells were treated with MLN4924 at different concentrations and incubation times. The inhibition rate of cell growth was detected using the cell counting kit-8 （CCK-8） assay. Apoptosis was observed using Hoechst 33342 and flow cytometry. The protein expression of the associated proteins in cell apoptosis, including caspase-3, NF-KB p65, and CDT1, was determined through Westem blot analysis. Results： The proliferation ofA549 cells decreased when the concentration of MLN4924 increased or the incubation time was prolonged. MLN4924 induced S phase cell cycle arrest. The protein expression of the associated proteins caspase-3 and CDT1 was higher than that of the control group. NF-KB p65 was lower than that in the control group. Conclusion： MLN4924 effectively inhibited the proliferation and induced cell apoptosis in A549 cells. MLN4924 treatment induced the S phase cell cycle arrest, increased the caspase-3 protein expression, and inhibited the NF-kB pathway activation.