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

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.

• Authors: 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
• Journal: PloS one (PLoS One) Vol. 9 Issue 7 Pg. e103304 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25068796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoxia-Inducible Factor 1, alpha Subunit
• Aryl Hydrocarbon Receptor Nuclear Translocator

Topics

• Apoptosis (genetics)
• Aryl Hydrocarbon Receptor Nuclear Translocator (genetics, metabolism)
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Cell Hypoxia
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic
• Hep G2 Cells
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• Immunoblotting
• Liver Neoplasms (genetics, metabolism, pathology)
• RNA Interference
• Reverse Transcriptase Polymerase Chain Reaction