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目的:探讨组蛋白去乙酰化酶抑制剂曲古霉素A(trichostatin A,TSA)对人非小细胞肺癌(NSCLC)A549细胞增殖抑制作用及机制。方法:以不同剂量TSA(0.1μM,0.5μM和1μM)处理A549细胞。MTT法检测细胞增殖情况,碘化丙啶(PI)染色结合流式细胞仪检测细胞周期,Western blot法检测P21蛋白表达,流式细胞仪检测细胞线粒体膜电位和细胞凋亡。结果:TSA剂量依赖性抑制肺癌A549细胞增殖,表现为细胞周期阻滞于G2/M期,同时P21蛋白表达增高;此外,TSA还可以剂量依赖性的促进A549细胞凋亡,伴有线粒体膜电位下降。结论:TSA促进NSCLCA549细胞周期阻滞和凋亡,从而抑制其增殖。
Objective: To investigate the inhibitory effect of histone deacetylase inhibitor trichostatin A (TSA) on the proliferation of human non-small cell lung cancer (NSCLC) A549 cells and its mechanism. Methods: A549 cells were treated with different doses of TSA (0.1 μM, 0.5 μM and 1 μM). The cell proliferation was detected by MTT assay. The cell cycle was detected by propidium iodide (PI) staining combined with flow cytometry. The expression of P21 protein was detected by Western blot. The mitochondrial membrane potential and cell apoptosis were detected by flow cytometry. Results: TSA inhibited the proliferation of A549 cells in a dose-dependent manner. The cell cycle arrest was in G2 / M phase and the expression of P21 protein was increased. In addition, TSA could also induce A549 cell apoptosis in a dose-dependent manner with mitochondrial membrane potential decline. Conclusion: TSA can promote cell cycle arrest and apoptosis of NSCLCA549 cells and inhibit its proliferation.