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背景与目的:多项研究表明组蛋白去乙酰化酶(histone deacetylases,HDACs)抑制剂对人非小细胞肺癌细胞株有抑制增殖和诱导凋亡作用。而HDAC抑制剂对HDACⅠ型和Ⅱ型均有抑制作用,在非小细胞肺癌细胞株中尚未明确HDACs中哪一类受抑制能影响肿瘤生长。本研究通过HDAC1siRNA转染肺腺癌细胞株A549,观察HDACs中HDAC1对肺腺癌细胞增殖、周期和凋亡的影响,明确HDAC1在肺腺癌细胞生长中的作用。方法:MTT法检测不同时间点HDAC1siRNA转染对A549细胞体外增殖的影响,流式细胞术检测RNA干扰后细胞周期及凋亡率的变化;Westernblot法检测细胞内组蛋白H4乙酰化水平的变化。结果:HDAC1siRNA转染A549细胞后,HDAC1在转录和表达水平均下降,组蛋白H4乙酰化表达增高。siRNA干扰后A549细胞的体外生长抑制呈时间依赖性,流式细胞术检测结果显示细胞阻滞于G2/M期,细胞凋亡增加。结论:HDAC1siRNA转染能有效地抑制HDAC1在A549细胞中的表达,增加A549细胞中组蛋白的乙酰化,并影响A549细胞相关生物学行为,抑制肺腺癌细胞的生长,为HDAC1基因治疗应用于肺腺癌奠定了基础。
BACKGROUND & AIM: Several studies have demonstrated that histone deacetylases (HDACs) inhibitors can inhibit proliferation and induce apoptosis in human non-small cell lung cancer cell lines. While HDAC inhibitors have inhibitory effects on both HDAC type I and type II, and it is unclear which of the HDACs in non-small cell lung cancer cell lines inhibits tumor growth. In this study, HDAC1 siRNA transfected lung adenocarcinoma cell line A549, in HDACs observed HDAC1 lung adenocarcinoma cell proliferation, cycle and apoptosis, clear HDAC1 in lung adenocarcinoma cell growth. Methods: MTT assay was used to detect the effect of HDAC1 siRNA transfection on the proliferation of A549 cells in vitro. Flow cytometry was used to detect the changes of cell cycle and apoptosis after RNA interference. Western blotting was used to detect the change of histone H4 acetylation. Results: HDAC1 siRNA transfected A549 cells, HDAC1 transcription and expression levels were decreased, histone H4 acetylation expression increased. The growth inhibition of A549 cells in vitro was time-dependent. The results of flow cytometry showed that the cells arrested in G2 / M phase and the apoptosis increased. Conclusion: HDAC1 siRNA transfection can effectively inhibit the expression of HDAC1 in A549 cells, increase the acetylation of histone in A549 cells and affect the biological behavior of A549 cells, inhibit the growth of lung adenocarcinoma cells, Lung adenocarcinoma laid the foundation.