부산대학교 도서관

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. [ABSTRACT FROM AUTHOR]