Hypoxia is the condition where tumor cells have been deprived of oxygen and has been shown to have a role of tumor development in the hepatocellular carcinoma (HCC). Using PubMed online database and Google scholar web site, the terms “angiogenesis”, “apoptosis”, “RNA interference” and/or “hepatocellular carcinoma (HCC)” were searched and analyzed. The hypoxia inducible factors (HIFs) are transcriptional regulators that affect a homeostatic response to oxidative stress and have been identified as a key transcription activator of angiogenesis, survival, and metabolism. Cytokines, such as IL-8, also controlled endothelia cells survival and angiogenesis. IL-8 was also overexpressed under hypoxia and induced tumor angiogenesis and growth. Therefore, regulation of HIFs and IL-8 controlled the tumor microenvironment in terms of tumor angiogenesis and apoptosis. The review summarizes the results of regulation of the hypoxic tumor environment.
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