【摘要】 研究组蛋白脱乙酰酶抑制剂MS275与polo样激酶1抑制剂BI2536联合作用对人非小细胞肺癌细胞株A549细胞的增效作用及其作用机制。采用CCK-8法检测MS275和BI2536单用或联用时对A549细胞增殖的影响,结果显示细胞增殖抑制率在两药联合作用后比单独用药作用显著增强;使用流式细胞仪检测细胞周期,表明联合用药时细胞被大量阻断在G2/M期。应用蛋白质免疫印迹法(western blot)检测蛋白激酶AKT和半胱氨酸蛋白水解酶caspase-3蛋白表达水平,显示细胞内激活的caspase-3切割片段增多,磷酸化蛋白激酶AKT表达量下调。研究结果提示,MS275协同BI2536阻断细胞周期,抑制A549细胞增殖,其作用机制应是通过上调caspase-3的活性,抑制蛋白激酶AKT磷酸化,影响PI3K/AKT通路来完成的。这两种药物的联合应用可能成为人非小细胞肺癌治疗中的新方案。更多还原

【Abstract】 The objective of this study was to determine if the combination of a promising histone deacetylase inhibitor MS-275 and a novel polo-like kinase 1 inhibitor BI2536 would show the enhanced antineoplastic activity on human A549 non-small-cell lung cancer cell and also to decipher the molecular mechanisms of action.The cell viability was examined by cell counting Kit-8(CCK8) assay and the flow cytometry was used to detect the cell cycle arrest.The combination of MS275 and BI2536 was found to be synergistic in inhibiting A549 cell growth,caused cell cytostaticity/cytotoxicity and induced marked G2/M phase arrest.Further more the western blot was introduced to evaluate the expression levels of phospho-AKT and caspase-3,and the results showed that after the treatment of MS275 and BI2536,caspase-3 was up regulated and phospho-AKT was down regulated.These results suggest that the mechanism of action is possibly through the activity of caspase-3 and inactivity of PI3K/AKT pathway.MS275/BI2536 regimen may represent a potential novel therapeutic strategy for Non-Small-Cell lung cancer.更多还原