Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Histone Deacetylase Inhibitor Trichostatin A Enhances Antitumor Effects of Docetaxel or Erlotinib in A549 Cell Line

  • Zhang, Qun-Cheng (Department of Pulmonary Medicine, Henan Provincial People's Hospital) ;
  • Jiang, Shu-Juan (Department of Respiratory (or Pulmonary) Medicine, Provincial Hospital of Shandong and Affiliated Hospital of Shandong University) ;
  • Zhang, Song (Department of Respiratory (or Pulmonary) Medicine, Provincial Hospital of Shandong and Affiliated Hospital of Shandong University) ;
  • Ma, Xiao-Bin (Department of Respiratory (or Pulmonary) Medicine, Provincial Hospital of Shandong and Affiliated Hospital of Shandong University)
  • Published : 2012.07.31
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Abstract

Background and 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 ${\alpha}$-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 $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-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.

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References

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