title: Histone deacetylase inhibitor trichostatin A enhances anti-tumor effects of docetaxel or erlotinib in A549 cell line.
abstract: OBJECTIVE
  Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells.
  
  
  METHODS
  A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to 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.
  
  
  RESULTS
  Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the G2/M transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of α-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90.
  
  
  CONCLUSIONS
  Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.
authors.affiliation: Department of Pulmonary Medicine, Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Qun-Cheng
authors.initials: QC
authors.lastname: Zhang
authors.forename: Shu-Juan
authors.initials: SJ
authors.lastname: Jiang
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Ma
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004357:Drug Synergism; D066246:ErbB Receptors / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D016195:G2 Phase / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011799:Quinazolines; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel; C012589:trichostatin A; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D053148:Caspase 3