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Inhibition of tumour angiogenesis and growth by small hairpin HIF ‐1α and IL ‐8 in hepatocellular carcinoma
Author(s) -
Choi Sung Hoon,
Kwon OhJoon,
Park Jun Yong,
Kim Do Young,
Ahn Sang Hoon,
Kim Seung Up,
Ro Simon Weonsang,
Kim Kyung Sik,
Park Jeon Han,
Kim Seungtaek,
Yun ChaeOk,
Han KwangHyub
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12375
Subject(s) - gene knockdown , angiogenesis , cancer research , small hairpin rna , vascular endothelial growth factor , cell growth , hypoxia inducible factors , biology , cell culture , chemistry , vegf receptors , gene , biochemistry , genetics
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 (sh RNA ) 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 sh RNA ‐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 sh RNA ‐induced HIF ‐1α and IL ‐8 knockdown inhibit angiogenesis and tumour growth in HCC . Further development of HIF ‐1α and IL ‐8 sh RNA technologies could lead to effective therapies for HCC .