title: Effects of trichostatin A on HIF-1α and VEGF expression in human tongue             squamous cell carcinoma cells in vitro.
abstract: Hypoxia is an essential feature of the microenvironment of solid tumors, which regulates a variety of transcription factors including hypoxia-inducible factor-1α (HIF-1α). HIF-1α overexpression enhances tumor angiogenesis via upregulation of vascular endothelial growth factor (VEGF) and some other hypoxia-inducible angiogenic factors, which lead to a more aggressive tumor phenotype, tumor metastasis and resistance to radiation and chemotherapy. In this study, we found that a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), inhibited cell proliferation and invasion, blocked the cell cycle, and induced cell apoptosis in a dose- and time-dependent manner in the human tongue squamous cell carcinoma (TSCC) SCC-6 cell line in vitro. Furthermore, TSA reduced both basal levels and hypoxia-induced HIF-1α protein accumulation but not HIF-1α mRNA levels, and both protein and mRNA levels of VEGF expression. These results showed that TSA had a potent anticancer activity on TSCC cells, suggesting that TSA could be a promising drug targeting tumor angiogenesis via inhibition of HIF-1α and VEGF expression in the development of an effective chemopreventive and anticancer agent on human TSCCs.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Tongji University, Shanghai 200072, PR China.
authors.forename: Fei-Wu
authors.initials: FW
authors.lastname: Kang
authors.forename: Lin
authors.initials: L
authors.lastname: Que
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Zuo-Lin
authors.initials: ZL
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell; D059447:Cell Cycle Checkpoints; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D014062:Tongue Neoplasms; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C012589:trichostatin A