目的：研究曲古抑菌素A（trichostatin A，TSA）联合多西他赛（docetaxel，Doc）对肺腺癌细胞A549凋亡的影响及其分子机制。方法：TSA单独或联合Doc处理A549细胞，MTT法检测A549细胞的增殖，光学显微镜下观察A549细胞的形态学变化，Hoechst 33258染色及流式细胞术检测A549细胞的凋亡，流式细胞术检测细胞周期的变化，Western blotting检测乙酰化α微管蛋白（acetylαtubulin）、survivin蛋白的表达及caspase3的活化。结果：10 μg/ml Doc、250 nmol/L TSA单独或联合作用均能时间依赖性地抑制A549细胞的增殖，联合作用的抑制率显著高于Doc或TSA单独作用\[(65.6±3.1)% vs (306±2.1)%、 (23.3±1.9)%, P<0.05\]。TSA、Doc单独或联合用药均可使A549细胞凋亡率增加，联合作用的凋亡率显著高于单独作用\[(58±3.6)% vs (17±2.2)%、(14±1.6)%，P<0.05\]。联合作用比单独作用使A549细胞更明显地阻滞于G2/M期\[(32.4±3.1)% vs (23.5±2.3)%、 (10.5±1.5)%，P<0.05\]。TSA联合Doc可进一步增加acetylαtubulin 表达、减少survivin蛋白的表达，并促进casapase3的活化（均P<0.05）。结论：TSA联合Doc能够抑制A549细胞的增殖、促进细胞的凋亡，其机制可能与上调acetylαtubulin 的表达、抑制survivin的表达以及促进caspase3活化有关。

Objective:To explore the effects of trichostatin A (TSA) and docetaxel (Doc) on apoptosis of lung adenocarcinoma A549 cells and the possible molecular mechanisms. Methods: A549 cells were treated with TSA alone or in combination with Doc, MTT assay was used to measure the proliferation of A549 cells; cell morphological changes were observed under light microscope; apoptosis was assessed using Hoechst 33258 staining and flow cytometry; cell cycle was analyzed by flow cytometry; the expression of acetylαtubulin and survivin protein and activation of caspase3 were detected by Western blotting. Results: 10 μg/ml Doc and 250 nmol/L TSA alone or in combination significantly inhibited the growth of A549 cells in a timedependent manner, and the combined treatment induced even higher inhibitory rate (\[656±31\]% vs \[30.6±2.1\]%, \[23.3±1.9\]%, P<0.05). In addition, TSA or Doc alone or in combination increased the apoptosis rate of A549 cells, and the combined treatment also induced higher apoptosis rate (\[58±3.6\]% vs \[17±2.2\]%, \[14±1.6\]%, P<0.05). The cell cycle was more markedly arrested in G2/M phase in combination treatment group (\[32.4±3.1\]% vs \[23.5±2.3\]%, \[10.5±1.5\]%, P<0.05), TSA combined with Doc increased the expression of acetylαtubulin, reduced the expression of survivin and promoted the activation of caspase3 (P<005). Conclusion: TSA combined with Doc can inhibit proliferation and induce apoptosis of A549 cells, which is related to the upregulation of acetylαtubulin, downregulation of survivin and increased activation of caspase3.

山东省卫生厅科研基金资助项目（No.32009）；山东省科技发展计划资助项目(No.2010G0020227)