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Knockdown of HIF-1a and IL-8 induced apoptosis of hepatocellular carcinoma triggers apoptosis of vascular endothelial cells

Authors
 Sung Hoon Choi  ;  Jun Yong Park  ;  Wonseok Kang  ;  Seung Up Kim  ;  Do Young Kim  ;  Sang Hoon Ahn  ;  Simon Wonsang Ro  ;  Kwang-Hyub Han 
Citation
 Apoptosis, Vol.21(1) : 85-95, 2016 
Journal Title
 Apoptosis 
ISSN
 1360-8185 
Issue Date
2016
MeSH
Adenoviridae/genetics ; Adenoviridae/metabolism ; Apoptosis/drug effects* ; Apoptosis/genetics ; Caspase 3/genetics ; Caspase 3/metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Culture Media, Conditioned/pharmacology ; Cytochromes c/secretion ; DNA Fragmentation ; Gene Expression Regulation, Neoplastic* ; Genetic Vectors/chemistry ; Genetic Vectors/metabolism ; Hep G2 Cells ; Human Umbilical Vein Endothelial Cells/cytology ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Interleukin-8/antagonists & inhibitors ; Interleukin-8/genetics* ; Interleukin-8/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Signal Transduction ; bcl-X Protein/genetics* ; bcl-X Protein/metabolism
Keywords
Apoptosis ; Death signal ligands ; FACs-TUNEL ; Hypoxia inducible factor-1α ; Interleukin-8 ; Tumor xenograft model
Abstract
A local hypoxic microenvironment is one of the most important characteristics of solid tumors. Hypoxia inducible factor-1α (HIF-1α) and Interleukin-8 (IL-8) activate tumor survival from hypoxic-induced apoptosis in each pathway. This study aimed to evaluate whether knockdown of HIF-1α and IL-8 induced apoptosis of the hepatocellular carcinoma (HCC) and endothelial cell lines. HCC cell lines were infected with adenovirus-expressing shRNA for HIF-1α and IL-8 and maintained under hypoxic conditions (1% O2, 24 h). The expression levels of HIF-1α and both apoptotic and growth factors were examined by real-time quantitative PCR and western blot. We also investigated apoptosis by TUNEL assay (FACS and Immunofluorescence) and measured the concentration of cytochrome C. Inhibition of HIF-1α and IL-8 up-regulated the expression of apoptotic factors while downregulating anti-apoptotic factors simultaneously. Knockdown of HIF-1α and IL-8 increased the concentration of cytochrome C and enhanced DNA fragmentation in HCC cell lines. Moreover, culture supernatant collected from the knockdown of HIF-1α and IL-8 in HCC cell lines induced apoptosis in human umbilical vein endothelial cells under hypoxia, and the expression of variable apoptotic ligand increased from HCC cell lines, time-dependently. These data suggest that adenovirus-mediated knockdown of HIF-1α and IL-8 induced apoptosis in HCC cells and triggered apoptosis of vascular endothelial cells.
Full Text
http://link.springer.com/article/10.1007/s10495-015-1185-2
DOI
10.1007/s10495-015-1185-2
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Liver Cirrhosis Clinical Research Center (간경변증임상연구센터) > 1. Journal Papers
Yonsei Authors
강원석(Kang, Won Suk)
김도영(Kim, Do Young)
김승업(Kim, Seung Up) ORCID logo https://orcid.org/0000-0002-9658-8050
노원상(Ro, Simon Weonsang) ORCID logo https://orcid.org/0000-0003-2187-3698
박준용(Park, Jun Yong) ORCID logo https://orcid.org/0000-0001-6324-2224
안상훈(Ahn, Sang Hoon) ORCID logo https://orcid.org/0000-0002-3629-4624
한광협(Han, Kwang-Hyub) ORCID logo https://orcid.org/0000-0003-3960-6539
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146291
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