title: HIF-1 Dimerization Inhibitor Acriflavine Enhances Antitumor Activity of Sunitinib in Breast Cancer Model.
abstract: 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.
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.forename: Sisi
authors.initials: S
authors.lastname: He
authors.forename: Guobo
authors.initials: G
authors.lastname: Shen
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000167:Acriflavine / Q000627:therapeutic use*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D007211:Indoles / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000166:cytology; D009336:Necrosis / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D055503:Protein Multimerization / Q000187:drug effects; D011758:Pyrroles / Q000627:therapeutic use*; D013154:Spleen / Q000166:cytology; D000077210:Sunitinib; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D051793:Hypoxia-Inducible Factor 1; D007211:Indoles; D011758:Pyrroles; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000167:Acriflavine; D000077210:Sunitinib