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 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.
BACKGROUND AND OBJECTIVE: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of humanmalignancies. 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 humanlung cancer.
Authors: Aaron P Havas; Kameron B Rodrigues; Anvi Bhakta; Joseph A Demirjian; Seongmin Hahn; Jack Tran; Margarethakay Scavello; Ana A Tula-Sanchez; Yi Zeng; Monika Schmelz; Catharine L Smith Journal: Cancer Biol Ther Date: 2016-10-28 Impact factor: 4.742
Authors: Yanmei Hao; Hongmei Yin; Chaomang Zhu; Feng Li; Yingjie Zhang; Yuyun Li; Xiaojing Wang; Duojie Li Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2019-07-30