Effects of the knockdown of hypoxia inducible factor-1alpha expression by adenovirus-mediated shRNA on angiogenesis and tumor growth in hepatocellular carcinoma cell lines.
10.3350/kjhep.2010.16.3.280
- Author:
Sung Hoon CHOI
1
;
Hye Won SHIN
;
Jun Yong PARK
;
Ji Young YOO
;
Do Young KIM
;
Weon Sang RO
;
Chae Ok YUN
;
Kwang Hyub HAN
Author Information
1. Brain Korea 21 project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Angiogenesis;
Hypoxia-inducible factor-1alpha (HIF-1alpha);
Small hairpin RNA (shRNA);
Human umbilical vein endothelial cells (HUVECs);
Hepatocellular carcinoma
- MeSH:
Adenoviridae/genetics;
Carcinoma, Hepatocellular/*blood supply/metabolism/therapy;
Cell Line, Tumor;
Cell Proliferation;
Endothelial Cells/metabolism;
Gene Knockdown Techniques;
Genetic Vectors;
Humans;
Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists &;
Liver Neoplasms/*blood supply/metabolism/therapy;
Matrix Metalloproteinases/metabolism;
Neovascularization, Pathologic/genetics/metabolism/*therapy;
RNA Interference;
RNA, Small Interfering/metabolism
- From:The Korean Journal of Hepatology
2010;16(3):280-287
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND/AIMS: Hypoxia-inducible factor-1alpha (HIF-1alpha) 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-1alpha (shHIF-1alpha) inhibits cell proliferation and angiogenesis in hepatocellular carcinoma (HCC) cell lines. METHODS: Knockdown of HIF-1alpha expression was constructed by adenovirus-mediated RNA interference tools, and HCC cell lines infected with shHIF-1alpha coding virus were cultured under a hypoxia condition (1% O2) for 24 hours. Following infection, the expression levels of HIF-1alpha, 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-1alpha 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-1alpha-infected groups in human umbilical vein endothelial cells (HUVECs). CONCLUSIONS: These data suggest that adenovirus-mediated inhibition of HIF-1alpha inhibits the invasion, tube formation, and cell growth in HUVECs and HCC cells.
