title: Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice.
abstract: OBJECTIVE
  Renal cell carcinoma (RCC) is the most frequent type of cancer among renal neoplasms in adults and responds poorly to radiotherapy and chemotherapy. There is evidence that blockade of the renin-angiotensin system (RAS) might have antineoplastic effects. The aim of this study was to investigate the effects of RAS blockade on RCC in a murine model.
  
  
  METHODS
  Murine renal cancer cells (Renca) were injected (1 × 10(5)) into the subcapsular space of the left kidney of BALB/c mice (8 wk of age). The animals were divided into 4 groups: a control group (no treatment), angiotensin-receptor blockers group (losartan 100mg/kg/d), angiotensin-converting enzyme inhibitor group (captopril 10mg/kg/d), and angiotensin-receptor blockers +angiotensin-converting enzyme inhibitor group (losartan 100mg/kg/d +captopril 10mg/kg/d). The animals received the drugs by gavage for 21 days after inoculation, beginning 2 days before tumor induction, and were then euthanized. After killing the animals, the kidneys and lungs were removed, weighed, and processed for histopathological and immunohistochemical analyses. Angiogenesis and vascular microvessels were assessed with the antibodies anti-vascular endothelial growth factor and anti-CD34.
  
  
  RESULTS
  Angiotensin II-inoculated animals developed renal tumors. Treated animals presented smaller tumors, regardless of the therapeutic regimen, and far fewer lung metastases in both quantity and dimension compared with the controls. The expression of vascular endothelial growth factor and CD34 were significantly decreased in renal tumors of treated animals compared with the controls.
  
  
  CONCLUSIONS
  Our findings suggest that blockade of RAS decreases tumor proliferation and metastatic capacity of RCC in this experimental model.
authors.affiliation: Department of Pathology, Universidade Federal de São Paulo (UNIFESP-EPM), São Paulo, Brazil. Electronic address: wedson.araujo@yahoo.com.br.
authors.forename: Wedson F
authors.initials: WF
authors.lastname: Araújo
authors.affiliation: Department of Medicine, Universidade Federal de São Paulo (UNIFESP-EPM), São Paulo, Brazil.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Naves
authors.affiliation: Department of Pathology, Universidade de São Paulo (USP), São Paulo, Brazil.
authors.forename: Juliana N
authors.initials: JN
authors.lastname: Ravanini
authors.affiliation: Department of Medicine, Universidade Federal de São Paulo (UNIFESP-EPM), São Paulo, Brazil.
authors.forename: Nestor
authors.initials: N
authors.lastname: Schor
authors.affiliation: Department of Pathology, Universidade Federal de São Paulo (UNIFESP-EPM), São Paulo, Brazil; Department of Medicine, Universidade Federal de São Paulo (UNIFESP-EPM), São Paulo, Brazil.
authors.forename: Vicente P C
authors.initials: VP
authors.lastname: Teixeira
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D002216:Captopril / Q000008:administration & dosage; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000473:pathology*; D019808:Losartan / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D019808:Losartan
keywords: Angiogenesis; Carcinoma; Immunohistochemistry; Pathologic; Renal cell; Renin-angiotensin system