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Effects of the knockdown of hypoxia inducible factor-1α expression by adenovirus-mediated shRNA on angiogenesis and tumor growth in hepatocellular carcinoma cell lines

Authors
 Sung Hoon Choi  ;  Hye Won Shin  ;  Jun Yong Park  ;  Ji Young Yoo  ;  Do Young Kim  ;  Weon Sang Ro  ;  Chae-Ok Yun  ;  Kwang-Hyub Han 
Citation
 Korean Journal of Hepatology (대한간학회지), Vol.16(3) : 280-287, 2010 
Journal Title
 Korean Journal of Hepatology (대한간학회지) 
ISSN
 1226-0479 
Issue Date
2010
MeSH
Adenoviridae/genetics ; Carcinoma, Hepatocellular/blood supply* ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/therapy ; Cell Line, Tumor ; Cell Proliferation ; Endothelial Cells/metabolism ; Gene Knockdown Techniques ; Genetic Vectors ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Liver Neoplasms/blood supply* ; Liver Neoplasms/metabolism ; Liver Neoplasms/therapy ; Matrix Metalloproteinases/metabolism ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/therapy* ; RNA Interference ; RNA, Small Interfering/metabolism
Keywords
Angiogenesis ; Hypoxia-inducible factor-1α (HIF-1α) ; Small hairpin RNA (shRNA) ; Human umbilical vein endothelial cells (HUVECs) ; Hepatocellular carcinoma
Abstract
BACKGROUND/AIMS: Hypoxia-inducible factor-1α (HIF-1α) is a central transcriptional factor involved in the cellular responses related to various aspects of cancer biology, including proliferation, survival, and angiogenesis, and the metabolism of the extracellular matrix in hypoxia. This study evaluated whether adenovirus-mediated small hairpin RNA (shRNA) against HIF-1α (shHIF-1α) inhibits cell proliferation and angiogenesis in hepatocellular carcinoma (HCC) cell lines. METHODS: Knockdown of HIF-1α expression was constructed by adenovirus-mediated RNA interference tools, and HCC cell lines infected with shHIF-1α coding virus were cultured under a hypoxia condition (1% O2) for 24 hours. Following infection, the expression levels of HIF-1α, angiogenesis factors, and matrix metalloproteinase (MMP) were examined using Western blotting. Cell proliferation and angiogenesis were measured by a cell proliferation assay (MTT assay) and an angiogenesis-related assay (invasion and tube-formation assay), respectively. RESULTS: Adenovirus mediated inhibition of HIF-1α induced suppression of tumor growth in HCC cell lines. It also down-regulated the expression of angiogenesis factor and MMP proteins. Angiogenesis as well as mobility of vascular cells to tumor was suppressed by adenovirus-mediated shHIF-1α-infected groups in human umbilical vein endothelial cells (HUVECs). CONCLUSIONS: These data suggest that adenovirus-mediated inhibition of HIF-1α inhibits the invasion, tube formation, and cell growth in HUVECs and HCC cells.
Files in This Item:
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DOI
10.3350/kjhep.2010.16.3.280
Appears in Collections:
5. Research Institutes (연구소) > Liver Cirrhosis Clinical Research Center (간경변증임상연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Do Young(김도영)
Ro, Simon Weonsang(노원상) ORCID logo https://orcid.org/0000-0003-2187-3698
Park, Jun Yong(박준용) ORCID logo https://orcid.org/0000-0001-6324-2224
Shin, Hye Won(신혜원)
Yoo, Ji Yeong(유지영)
Yun, Chae Ok(윤채옥)
Choi, Sung Hoon(최성훈)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/101851
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