Hypoxia, which arises in tumor cells that have been deprived of oxygen, has been shown to play a role in tumor development in hepatocellular carcinoma. Hypoxia-inducible factors (HIFs) are transcription factors that regulate cellular homeostatic responses to oxidative stress and have been identified as key transcriptional activators of tumor angiogenesis, survival, and metabolism. Cytokines, such as IL-8, also influence survival and angiogenesis in endothelial cells. IL-8 is overexpressed under hypoxic conditions and has been demonstrated to induce tumor angiogenesis and growth. Regulation of these oncological factors using RNA interference-based tools, small interfering RNA (siRNA) and short hairpin RNA (shRNA), were investigated in vitro and in vivo. The conclusion based on multiple studies is that regulation of HIFs and IL-8 by si/shRNA results in modulation of tumor angiogenesis and apoptosis in the tumor microenvironment. This review summarizes the results of studies investigating regulation of the hypoxic tumor environment.
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