Silencing of hypoxia-inducible factor-1? induces anti-tumor effects in hepatoma cell lines under tumor hypoxia.

ABSTRACT: Dimerization of hypoxia-inducible factor-1 beta (HIF-1?) [aryl hydrocarbon receptor nuclear translocator (ARNT)] with HIF-1? is involved in various aspects of cancer biology, including proliferation and survival under hypoxic conditions. We investigated the in vitro mechanism by which silencing of HIF-1? leads to the suppression of tumor cell growth and cellular functions. Various hepatocellular carcinoma (HCC) cell lines (Huh-7, Hep3B, and HepG2) were transfected with small interfering RNA (siRNA) against HIF-1? (siHIF-1?) and cultured under hypoxic conditions (1% O2 for 24 h). The expression levels of HIF-1?, HIF-1?, and growth factors were examined by immunoblotting. Tumor growth was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and tumor activity was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling, tumor cell invasion, and migration assays. Under hypoxic conditions, silencing of HIF-1? expression suppressed tumor cell growth and regulated the expression of tumor growth-related factors, such as vascular endothelial growth factor, epidermal growth factor, and hepatocyte growth factor. Suppression of tumor cell invasion and migration was also demonstrated in HIF-1?-silenced HCC cell lines. Silencing of HIF-1? expression may induce anti-tumor effects under hypoxic conditions in HCC cell lines.

SUBMITTER: Choi SH 

PROVIDER: S-EPMC4113399 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature