The cytotoxicity of histone deacetylase inhibitor plus paclitaxel to lung cancer cells / 解放军医学杂志

ABSTRACT

Objective To evaluate the cytotoxicity of trichostatin A (TSA),a histone deacetylase inhibitor,plus paclitaxel to H1299 strain lung cancer cells. Methods H1299 cells were exposed to TSA and/or paclitaxel in different concentrations in different ways. The proliferation rates were determined by MTT assay,the 50% inhibition concentration (IC50) of paclitaxel was calculated and the growth curve was plotted. The H1299 cells were then divided into 4 groupscontrol group (cells were normally cultivated for 36h),TAX group (cells were treated with 10nmol/L of paclitaxel for 24h),TSA group (cells were treated with 300nmol/L of TSA for 24h) and TF group (cells were exposed to TAX for 24h after being treated with TSA). Cell cycle and apoptosis were determined by flow cytometry. The morphological changes in nuclei as stained with Hoechst 33342 were observed by fluorescence microscopy. The protein expression levels of p21 and cleaved poly-ADP ribose polymerase (PARP) were determined by Western blotting. Results TSA significantly enhanced the inhibition of paclitaxel in lung cancer cell lines H1299. When combined with TSA,the IC50 of paclitaxel decreased significantly from 110.6?38.7nmol/L to 63.7?11.8nmol/L in H1299 cells (P0.05). Conclusion The HDAC inhibitor TSA,combined with TAX,may enhance the cytotoxicity of paclitaxel to,and promote the death of,lung cancer cell line H1299,which may not be related to apoptosis.