Effect of trichostatin A and paclitaxel on the growth and apoptosis of lung adenocarcinoma cell lines

Abstract

To investigate the effect of trichostatin A (TSA)/paclitaxel on the growth and apoptosis in human lung adenocarcinoma cell line A549 cells. Human lung adenocarcinoma A549 cells were cultured in DMEM in the presence of paclitaxel and the histone deacetylase inhibitor trichostatin A, and the growth curve was obtained by trypan-blue exclusion assay and cell count. Apoptosis was assessed using Hoechst 33258 staining and flow cytometry, and cell cycle was detected by flow cytometry analysis. The proteins of PARP, caspase-3, survivin and tubulin acetylation were detected by Western blotting. Significant growth reduction was observed in the A549 cells following treatment with paclitaxel or the histone deacetylase inhibitor TSA. The combined treatment with TSA/paclitaxel caused the highest inhibition of cell growth. The apoptosis rate of A549 cells treated with TSA or paclitaxel for 24 hours was (17.6 ± 1.8)% and (39.2 ± 3.7)%, respectively, but a significantly higher apoptosis rate was (64.2 ± 4.2)% was induced by combined treatment with TSA and paclitaxel. In contrast with the control group, the cell cycle was markedly arrested at G2/M phase in the TSA and paclitaxel group (P < 0.05). The Western blot analysis demonstrated that treatment with TSA/paclitaxel led to a synergistic increase of acetylated tubulin, PARP and caspase-3, and reduced the expression of survivin. TSA or paclitaxel alone can inhibit the cell growth and induce apoptosis, and the combination of TSA and paclitaxel exerts a synergistic effect on the growth and apoptosis in lung adenocarcinoma cells.