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

Sung Hoon Choi, Ae Ri Chung, Wonseok Kang, Jun Yong Park, Mi Sol Lee, Shin Won Hwang, Do Young Kim, Seung Up Kim, Sang Hoon Ahn, Seungtaek Kim, Kwang Hyub Han

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8 Citations (Scopus)

Abstract

Dimerization of hypoxia-inducible factor-1 beta (HIF-1β) [aryl hydrocarbon receptor nuclear translocator (ARNT)] with HIF-1α 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-1β 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-1β (siHIF-1β) and cultured under hypoxic conditions (1% O2 for 24 h). The expression levels of HIF-1β, HIF-1α, 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-1β 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-1β-silenced HCC cell lines. Silencing of HIF-1β expression may induce anti-tumor effects under hypoxic conditions in HCC cell lines.

Original languageEnglish
Article numbere103304
JournalPloS one
Volume9
Issue number7
DOIs
Publication statusPublished - 2014 Jul 28

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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