Histone Deacetylase Inhibitor Trichostatin A Enhances Antitumor Effects of Docetaxel or Erlotinib in A549 Cell Line

Abstract

Background and <br/><b>Objective</b>: Histone deacetylase (HDAC) inhibitors represent a promising class of potentialanticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatinA (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent orerlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. <br/><b>Methods</b>: A549 cells were treated withTXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distributionwere evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employedto examine alterations of α-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR),and caspase-3 in response to the different exogenous stimuli. <br/><b>Results</b>: Compared with single-agent treatment,co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, inducedapoptosis, and caused cell cycle delay at the G2/M transition. Treatment with TSA/TXT or TSA/erlotinib ledto a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of α-tubulin orhsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90.<br/><b>Conclusions</b>: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancercells. Such combinations may provide a more effective strategy for treating human lung cancer.