Figure 7. Metformin administration suppressed hypoxia-induced abnormally excessive angiogenesis by ameliorating tumor hypoperfusion.

In the hypoxic region adjacent to tumor necrosis, hypoperfusion results in aberrant angiogenesis via hypoxia-induced increase in HIF-1α protein level. HIF-1α protein has the potential to up-regulate multiple pro-angiogenic factors, thus greatly enhancing the abilities of sprouting and branching of tumor vessels. Metformin suppresses the abnormally aberrant angiogenesis in tumor by inhibiting HIF-1α-induced expressions of pro-angigenic factors via increase of tumor perfusion.