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Trichostatin A combined with docetaxel promote apoptosis of lung adenocarcinoma cells and the possible molecular mechanisms
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Abstract:
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 acetylαtubulin and survivin protein and activation of caspase3 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 timedependent manner, and the combined treatment induced even higher inhibitory rate (\[656±31\]% 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 G2/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 acetylαtubulin, reduced the expression of survivin and promoted the activation of caspase3 (P<005). Conclusion: TSA combined with Doc can inhibit proliferation and induce apoptosis of A549 cells, which is related to the upregulation of acetylαtubulin, downregulation of survivin and increased activation of caspase3.
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Project Supported:
Project supported by the Foundation from Health Department of Shandong Province (No.32009), and the Science and Technology Development Foundation of Shandong Province (No.2010G0020227)
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