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Effect of trichostatin A and paclitaxel on the proliferation and apoptosis of lung adenocarcinoma cells
Background Histone deacetylase inhibitors can regulate gene expression through modulation of the degree of acetylation of histone and non-histone, thus affecting cell proliferation, survival and chemosensitivity. Histone deacetylase inhibitors combined with paclitaxel may enhance the inhibitory effe...
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Published in: | Chinese medical journal 2013-01, Vol.126 (1), p.129-134 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Background Histone deacetylase inhibitors can regulate gene expression through modulation of the degree of acetylation of histone and non-histone, thus affecting cell proliferation, survival and chemosensitivity. Histone deacetylase inhibitors combined with paclitaxel may enhance the inhibitory effect of drugs on lung cancer cells. This study aimed to observe the effect of trichostatin A (TSA)/paclitaxel on the proliferation and apoptosis in human A549 lung adenocarcinoma cells, and to investigate its mechanism. Methods A549 cells were cultured in Dulbecco modified Eagle's medium (DMEM) in the presence of paclitaxel and the histone deacetylase inhibitor TSA, and the growth curve was obtained by trypan-blue exclusion assay and cell count. Apoptosis was assessed using Hoechst 33258 staining and flow cytometry analysis, and cell cycle was detected by flow cytometry analysis. The proteins poly ADP-ribose polymerase (PARP), caspase-3, survivin, and tubulin acetylation were detected by Western blotting. Results A significant reduction of proliferation was observed in A549 lung adenocarcinoma cells treated by paclitaxel or TSA. Combined treatment with TSA/paclitaxel caused the greatest inhibition of cell proliferation. The combined treatment with TSA and paclitaxel induced more severe apoptosis, and significantly more cells were arrested in G2/M phase (P 〈0.05) then with a single drug. Using Western blotting, we demonstrated that treatment with TSNpaclitaxel led to synergistic increase in acetylated tubulin, PARP, caspase-3, and reduced the expression of survivin. Conclusion TSA and paclitaxel have a synergistic activity that can inhibit cell growth and induce apoptosis. |
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ISSN: | 0366-6999 2542-5641 |
DOI: | 10.3760/cma.j.issn.0366-6999.20120009 |