Angiotensin II type 1 receptor antagonists inhibit cell proliferation and angiogenesis in breast cancer

Xuesong Chen; Qingwei Meng; Yanbin Zhao; Meiyan Liu; Dandan Li; Yanmei Yang; Lichun Sun; Guangjie Sui; Li Cai; Xiaoqun Dong

doi:10.1016/j.canlet.2012.10.006

Angiotensin II type 1 receptor antagonists inhibit cell proliferation and angiogenesis in breast cancer

Cancer Lett. 2013 Jan 28;328(2):318-24. doi: 10.1016/j.canlet.2012.10.006. Epub 2012 Oct 22.

Authors

Xuesong Chen¹, Qingwei Meng, Yanbin Zhao, Meiyan Liu, Dandan Li, Yanmei Yang, Lichun Sun, Guangjie Sui, Li Cai, Xiaoqun Dong

Affiliation

¹ Department of Internal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin 150040, Heilongjiang Province, China.

PMID: 23092556
DOI: 10.1016/j.canlet.2012.10.006

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Angiogenesis Inhibitors / administration & dosage
Angiogenesis Inhibitors / pharmacology*
Angiotensin II Type 1 Receptor Blockers / administration & dosage
Angiotensin II Type 1 Receptor Blockers / pharmacology*
Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / pharmacology*
Breast Neoplasms / blood supply*
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects
Female
Gene Expression Regulation, Neoplastic / drug effects
Humans
Losartan / pharmacology
MCF-7 Cells
Mice
Mice, Nude
Middle Aged
Neovascularization, Pathologic / drug therapy
Neovascularization, Pathologic / metabolism*
Receptor, Angiotensin, Type 1 / genetics
Receptor, Angiotensin, Type 1 / metabolism*
Tumor Burden / drug effects
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism
Xenograft Model Antitumor Assays

Substances

Angiogenesis Inhibitors
Angiotensin II Type 1 Receptor Blockers
Antineoplastic Agents
Receptor, Angiotensin, Type 1
Vascular Endothelial Growth Factor A
Losartan