Department of Respiratory Diseases, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
Chin Med J (Engl). 2013 Jan;126(1):129-34.
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.
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.
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 TSA/paclitaxel led to synergistic increase in acetylated tubulin, PARP, caspase-3, and reduced the expression of survivin.
TSA and paclitaxel have a synergistic activity that can inhibit cell growth and induce apoptosis.
组蛋白去乙酰化酶抑制剂可通过调节组蛋白和非组蛋白的乙酰化程度来调节基因表达，从而影响细胞增殖、存活和化疗敏感性。组蛋白去乙酰化酶抑制剂与紫杉醇联合使用可能增强药物对肺癌细胞的抑制作用。本研究旨在观察曲古抑菌素 A（TSA）/紫杉醇对人 A549 肺腺癌细胞增殖和凋亡的影响，并探讨其机制。
用含紫杉醇和组蛋白去乙酰化酶抑制剂 TSA 的 DMEM 培养基培养 A549 细胞，用台盼蓝排斥试验和细胞计数法获得生长曲线。用 Hoechst 33258 染色和流式细胞术分析检测细胞凋亡，用流式细胞术检测细胞周期。用 Western blot 检测多聚 ADP-核糖聚合酶（PARP）、caspase-3、survivin 和微管蛋白乙酰化。
紫杉醇或 TSA 处理 A549 肺腺癌细胞后，增殖明显减少。 TSA/紫杉醇联合治疗导致细胞增殖抑制最为显著。 TSA 和紫杉醇联合治疗诱导的细胞凋亡更为严重，与单药治疗相比，G2/M 期细胞阻滞更为明显（P<0.05）。Western blot 结果表明， TSA/紫杉醇联合治疗导致乙酰化微管蛋白、PARP、caspase-3 协同增加，survivin 表达降低。
TSA 和紫杉醇具有协同作用，可抑制细胞生长并诱导细胞凋亡。
