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

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 
Citation
 PLOS ONE, Vol.9(7) : e103304, 2014 
Journal Title
 PLOS ONE 
Issue Date
2014
MeSH
Apoptosis/genetics ; Aryl Hydrocarbon Receptor Nuclear Translocator/genetics* ; Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/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 ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Immunoblotting ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; RNA Interference* ; Reverse Transcriptase Polymerase Chain Reaction
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.
Files in This Item:
T201405491.pdf Download
DOI
10.1371/journal.pone.0103304
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kang, Won Suk(강원석)
Kim, Do Young(김도영)
Kim, Seung Up(김승업) ORCID logo https://orcid.org/0000-0002-9658-8050
Kim, Seung Taek(김승택)
Park, Jun Yong(박준용) ORCID logo https://orcid.org/0000-0001-6324-2224
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
Lee, Mi Sol(이미솔)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/138706
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