 stress, several survival pathways in hypoxic tumor cells are activated to carry out those essential biological processes that differ from the processes of normal cells \[[@R2]\]. Hypoxia-inducible factor 1 (HIF-1) is an oxygen-sensitive transcription factor \[[@R3]\] comprised of α and β subunits that form a heterodimer that binds to the hypoxia response element (HRE) region in DNA \[[@R3]--[@R5]\]. HIF-1α controls the expression of downstream target genes, including glucose transporter 1 (GLUT1), vascular endothelial growth factor (VEGF), insulin growth factor 2 (IGF2), transforming growth factor (TGF), erythropoietin (EPO) and so on. HIF-1α is correlated with vascular density \[[@R6], [@R7]\], tumor metastasis, angiogenesis, poor patient prognosis, as well as anticancer drug resistance \[[@R2]\]. Under normoxic conditions, HIF-1α hydroxylation of proline residues within its oxygen-dependent degradation (ODD) domain allows for HIF-1α association with von Hippel--Lindau (VHL) protein. Then, HIF-1α is degraded by 26S proteasome \[[@R8], [@R9]\]. Additionally, anticancer efficacy is reduced by HIF-1α overexpression or hypoxic conditions, which leads to the induction of drug resistance \[[@R10], [@R11]\]. Tumor hypoxia also leads to resistance to radiotherapy \[[@R12]\]. However, it is unknown whether HIF-1α can induce drug resistance of histone deacetylase (HDAC) inhibitor trichostatin A (TSA).

TSA was first obtained from *Streptomyces hygroscopicus* as an antifungal antibiotic that is active against *Trichophyton* species and is used for the specific inhibition of HDACs including the class I and II, but not class III HDACs \[[@R13]\]. Highly acetylated histones are accumulated by TSA \[[@R14]\]. Reduced HDAC activity blocks the cell cycle, cell proliferation, and apoptosis \[[@R15]\]. TSA inhibits the hypoxia-induced accumulation of HIF-1α and VEGF under hypoxic conditions \[[@R16]--[@R19]\]. TSA also decreases HIF-1αlpha protein levels and VEGF expression in multiple cancer cells, including HeLa cell