title: Antiangiogenic and finasteride therapies: responses of the prostate microenvironment in elderly mice.
abstract: OBJECTIVE
  The aim of this study was to evaluate the structural and molecular effects of antiangiogenic therapies and finasteride on the ventral prostate of senile mice.
  
  
  METHODS
  90 male FVB mice were divided into: Young (18 weeks old) and senile (52 weeks old) groups; finasteride group: finasteride (20mg/kg); SU5416 group: SU5416 (6 mg/kg); TNP-470 group: TNP-470 (15 mg/kg,) and SU5416+TNP-470 group: similar to the SU5416 and TNP-470 groups. After 21 days, prostate ventral lobes were collected for morphological, immunohistochemical and Western blotting analyses.
  
  
  RESULTS
  The results demonstrated atrophy, occasional proliferative lesions and inflammatory cells in the prostate during senescence, which were interrupted and/or blocked by treatment with antiangiogenic drugs and finasteride. Decreased AR and endostatin reactivities, and an increase for ER-α, ER-β and VEGF, were seen in the senile group. Decreased VEGF and ER-α reactivities and increased ER-β reactivity were verified in the finasteride, SU5416 groups and especially in SU5416+TNP-470 group. The TNP-470 group showed reduced AR and ER-β protein levels.
  
  
  CONCLUSIONS
  The senescence favored the occurrence of structural and/or molecular alterations suggesting the onset of malignant lesions, due to the imbalance in the signaling between the epithelium and stroma. The SU5416+TNP-470 treatment was more effective in maintaining the structural, hormonal and angiogenic factor balance in the prostate during senescence, highlighting the signaling of antiproliferation via ER-β.
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Larissa Akemi
authors.initials: LA
authors.lastname: Kido
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Amanda Cia
authors.initials: AC
authors.lastname: Hetzl
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Eduardo Marcelo
authors.initials: EM
authors.lastname: Cândido
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Fabio
authors.initials: F
authors.lastname: Montico
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Raísa Mistieri
authors.initials: RM
authors.lastname: Lorencini
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil. Electronic address: quitete@unicamp.br.
authors.forename: Valéria Helena Alves
authors.initials: VH
authors.lastname: Cagnon
mesh_terms: D000367:Age Factors; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects* / Q000502:physiology; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D018120:Finasteride / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011467:Prostate / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D018120:Finasteride
keywords: Aging; Antiangiogenic; Finasteride; Hormone receptor; Prostate