Journal
HYPOXIA
Volume 5, Issue -, Pages 1-9Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/HP.S130526
Keywords
cancer progression; erythropoiesis; hypoxia-inducible factor; hypoxia-inducible factor prolyl hydroxylase inhibitors; vascular endothelial growth factor; MMTV-Neu breast cancer model
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The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neu(ndl)-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD; MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs), FG-4497 or roxadustat (FG-4592). In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors.
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