Knockdown of HIF-1α and IL-8 induced apoptosis of hepatocellular carcinoma triggers apoptosis of vascular endothelial cells
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- 作者：Sung Hoon Choi ; Jun Yong Park ; Wonseok Kang ; Seung Up Kim ; Do Young Kim…
- 关键词：Apoptosis ; Hypoxia inducible factor ; 1α ; Interleukin ; 8 ; Death signal ligands ; FACs ; TUNEL ; Tumor xenograft model
- 刊名：Apoptosis
- 出版年：2016
- 出版时间：January 2016
- 年：2016
- 卷：21
- 期：1
- 页码：85-95
- 全文大小：7,684 KB
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Jun Yong Park (1) (2) (3)
Wonseok Kang (1) (2)
Seung Up Kim (1) (2) (3)
Do Young Kim (1) (2) (3)
Sang Hoon Ahn (1) (2) (3)
Simon Wonsang Ro (1) (2)
Kwang-Hyub Han (1) (2) (3)
1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
2. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
3. Yonsei Liver Center, Yonsei University Health System, Seoul, Korea - 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Oncology
Cancer Research
Cell Biology
Biochemistry
Virology - 出版者：Springer Netherlands
- ISSN：1573-675X
文摘
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. Keywords Apoptosis Hypoxia inducible factor-1α Interleukin-8 Death signal ligands FACs-TUNEL Tumor xenograft model