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

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)632-642
Number of pages11
JournalLiver International
Volume34
Issue number4
DOIs
Publication statusPublished - 2014 Apr

All Science Journal Classification (ASJC) codes

  • Hepatology

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