Angiotensin-(1-7) Reduces Prostate Cancer Growth and Metastasis by Altering the Tumor Microenvironment

Ang-(1-7) is an endogenous peptide hormone that is produced in the circulation and in tissues by proteolytic cleavage of angiotensin I or II. The heptapeptide mediates biological responses by activating a unique G-protein-coupled angiotensin-(1-7) [AT(1-7)] receptor mas, thereby providing specific targeted actions when used as a therapeutic agent. In this study, athymic mice with human LNCaP xenografts were infused with saline or Ang-(1-7) (24 g/kg/h) for 54 days. The heptapeptide markedly reduced tumor volume and wet weight as compared to saline administration. Tumors from mice treated with Ang-(1-7) had a 78% reduction in Ki67 and a 55% decrease in the phosphorylation of the MAP kinases ERK1 and ERK2, compared to tumor tissue from Ang-(1-7)-medicated animals, suggesting that the heptapeptide reduces cell proliferation. A significant reduction in both LNCaP and PC3 cell growth was observed following incubation with 100 nM Ang-(1-7) in vitro, supporting the anti-proliferative properties of the heptapeptide. Mas was detected by Western blot hybridization in both cell types.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2011

Author dc:creator

• Krishnan, Bhavani

• Angiogenesis

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/33490

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/33490