曲古抑菌素A
生存素
细胞生长
组蛋白脱乙酰基酶
细胞凋亡
A549电池
紫杉醇
细胞周期
癌症研究
组蛋白脱乙酰酶抑制剂
化学
分子生物学
乙酰化
流式细胞术
生物
组蛋白
癌症
生物化学
基因
遗传学
作者
Song Zhang,Quncheng Zhang,Shujuan Jiang
标识
DOI:10.3760/cma.j.issn.0366-6999.20120009
摘要
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 G 2 /M phase ( P <0.05) then with a single drug. Using Western blotting, we demonstrated that treatment with TSA/paclitaxel 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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