Abstract
Angiotensin II type 1 receptor (AT1R) promotes tumor invasion, migration, metastasis and angiogenesis. We explored the potential antitumor effects of AT1R antagonists in breast cancer. We found that angiotensin II promoted cell proliferation and upregulated the expression of vascular endothelial growth factor A (VEGF-A) in MCF-7 cells. Losartan downregulated the expression of VEGF-A in MCF-7 cells treated with angiotensin II. Candesartan downregulated the expression of VEGF-A in mice bearing MCF-7 xenografts and inhibited tumor growth and angiogenesis. AT1R and VEGF-A expression correlated with increased microvascular density in 102 breast cancer patients. Our data suggest that AT1R antagonists might be useful to suppress breast cancer by inhibiting the angiotensin II.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Angiogenesis Inhibitors / administration & dosage
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Angiogenesis Inhibitors / pharmacology*
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Angiotensin II Type 1 Receptor Blockers / administration & dosage
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Angiotensin II Type 1 Receptor Blockers / pharmacology*
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Animals
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / pharmacology*
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Breast Neoplasms / blood supply*
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Breast Neoplasms / drug therapy
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Breast Neoplasms / metabolism*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Losartan / pharmacology
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MCF-7 Cells
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Mice
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Mice, Nude
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Middle Aged
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Neovascularization, Pathologic / drug therapy
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Neovascularization, Pathologic / metabolism*
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Receptor, Angiotensin, Type 1 / genetics
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Receptor, Angiotensin, Type 1 / metabolism*
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Tumor Burden / drug effects
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
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Xenograft Model Antitumor Assays
Substances
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Angiogenesis Inhibitors
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Angiotensin II Type 1 Receptor Blockers
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Antineoplastic Agents
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Receptor, Angiotensin, Type 1
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Vascular Endothelial Growth Factor A
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Losartan