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

 Sung Hoon Choi  ;  Jun Yong Park  ;  Wonseok Kang  ;  Seung Up Kim  ;  Do Young Kim  ;  Sang Hoon Ahn  ;  Simon Wonsang Ro  ;  Kwang-Hyub Han 
 APOPTOSIS, Vol.21(1) : 85-95, 2016 
Journal Title
Issue Date
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
Apoptosis ; Death signal ligands ; FACs-TUNEL ; Hypoxia inducible factor-1α ; Interleukin-8 ; Tumor xenograft model
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.
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 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
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
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
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