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Inhibition of tumour angiogenesis and growth by small hairpin HIF-1α and IL-8 in hepatocellular carcinoma.

 Sung Hoon Choi  ;  Oh Joon Kwon  ;  Jun Yong Park  ;  Do Young Kim  ;  Sang Hoon Ahn  ;  Seung Up Kim  ;  Simon Weonsang Ro  ;  Kyung Sik Kim  ;  Jeon Han Park  ;  Seungtaek Kim  ;  Chae Ok Yun  ;  Kwang Hyub Han 
 LIVER INTERNATIONAL, Vol.34(4) : 632-642, 2014 
Journal Title
Issue Date
Adenoviridae ; Animals ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/therapy* ; Gene Knockdown Techniques ; Genetic Therapy/methods* ; Genetic Vectors/genetics ; Human Umbilical Vein Endothelial Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Immunoblotting ; Interleukin-8/genetics* ; Liver Neoplasms/genetics ; Liver Neoplasms/therapy* ; Mice ; Neoplasm Invasiveness/physiopathology ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/physiopathology* ; Real-Time Polymerase Chain Reaction
angiogenesis ; hepatocellular carcinoma ; hypoxia inducible factor-1 alpha ; interleukin-8 ; tumour xenograft
BACKGROUND & AIMS: Hypoxia-inducible factor-1α (HIF-1α), a key transcription factor in the cellular response to hypoxia, and interleukin 8 (IL-8), a key mediator of angiogenesis, are important in cancerous tumour growth. In this study, we evaluated the effects of HIF-1α and IL-8 knockdown on angiogenesis and tumour growth in hepatocellular carcinoma (HCC).

METHODS: Hepatocellular carcinoma cell lines were infected with adenoviruses expressing small-hairpin RNA (shRNA) specific for HIF-1α or IL-8, cultured under hypoxic conditions (1% O2), and examined for their levels of HIF-1α, IL-8, and angiogenesis factors using immunoblot. The effects of adenovirus-mediated shRNA-induced HIF-1α and IL-8 knockdown on tumour growth and angiogenesis were also investigated in a subcutaneous Hep3B-tumour mouse model.

RESULTS: Hypoxia-inducible factor-1α knockdown directly repressed tumour growth, whereas IL-8 knockdown indirectly repressed tumour growth. Combined knockdown of HIF-1α and IL-8 increased survival rates of mice. HIF-1α and IL-8 knockdown also decreased microvessel density and tumour volume in vivo. Similarly, HIF-1α and IL-8 knockdown inhibited the angiogenic effects of HCC cell-conditioned media on tube formation and invasion by endothelial cells in vitro.

CONCLUSION: These findings indicate that shRNA-induced HIF-1α and IL-8 knockdown inhibit angiogenesis and tumour growth in HCC. Further development of HIF-1α and IL-8 shRNA technologies could lead to effective therapies for HCC.
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sik(김경식) ORCID logo https://orcid.org/0000-0001-9498-284X
Kim, Do Young(김도영)
Kim, Seung Up(김승업) ORCID logo https://orcid.org/0000-0002-9658-8050
Kim, Seung Taek(김승택)
Ro, Simon Weonsang(노원상) ORCID logo https://orcid.org/0000-0003-2187-3698
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
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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