HIF-1 Dimerization Inhibitor Acriflavine Enhances Antitumor Activity of Sunitinib in Breast Cancer Model

Antiangiogenic therapy is a promising strategy for cancer therapy. However, antiangiogenic therapy can induce intratumor hypoxia and hypoxia-inducible factor-1 (HIF-1) expression, which slows cancer progression. In our present study, we found that antiangiogenic therapy with sunitinib plus HIF-1 dimerization inhibitor acriflavine retarded tumor growth in a murine model of breast cancer. The combination of sunitinib with acriflavine significantly decreased vascular endothelial growth factor and TGF-β expression and reduced tumor vasculature followed by increased intratumor necrosis and apoptosis. Moreover, decreased accumulation of myeloid-derived suppressor cells in the spleen was observed after the combinational therapy. In conclusion, the combination of HIF-1 inhibition and antiangiogenic therapy may represent a novel strategy for cancer patients.