Title |
Knockdown of HIF-1α and IL-8 induced apoptosis of hepatocellular carcinoma triggers apoptosis of vascular endothelial cells
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Published in |
Apoptosis, October 2015
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DOI | 10.1007/s10495-015-1185-2 |
Pubmed ID | |
Authors |
Sung Hoon Choi, Jun Yong Park, Wonseok Kang, Seung Up Kim, Do Young Kim, Sang Hoon Ahn, Simon Wonsang Ro, Kwang-Hyub Han |
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. |
X Demographics
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
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Unknown | 13 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 3 | 23% |
Student > Ph. D. Student | 1 | 8% |
Lecturer | 1 | 8% |
Researcher | 1 | 8% |
Student > Postgraduate | 1 | 8% |
Other | 0 | 0% |
Unknown | 6 | 46% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 2 | 15% |
Agricultural and Biological Sciences | 2 | 15% |
Medicine and Dentistry | 2 | 15% |
Chemistry | 1 | 8% |
Unknown | 6 | 46% |