Antiangiogenic and finasteride therapies: Responses of the prostate microenvironment in elderly mice

Author(s)

Kido, Larissa Akemi ^[1] ; Hetzl, Amanda Cia ^[1] ; Candido, Eduardo Marcelo ^[1] ; Montico, Fabio ^[1] ; Lorencini, Raisa Mistieri ^[1] ; Alves Cagnon, Valeria Helena ^[1]

Affiliation

^[1] State Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, BR-13083865 Campinas, SP - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 106, n. 1-2, p. 58-70, JUN 13 2014.
• Web of Science Citations: 4

Abstract

Aims: 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. Main methods: 90 male FVB mice were divided into: Young (18 weeks old) and senile (52 weeks old) groups; finasteride group: finasteride (20 mg/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. Key findings: 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-alpha, ER-beta and VEGF, were seen in the senile group. Decreased VEGF and ER-a reactivities and increased ER-beta reactivity were verified in the finasteride, SU5416 groups and especially in SU5416 + TNP-470 group. The TNP-470 group showed reduced AR and ER-beta protein levels. Significance: 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-beta. (C) 2014 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 12/03010-4 - Molecular characterization of the prostate after hormonal and antiangiogenic therapies in senile mice (FVB) and in transgenic adenocarcinoma of mice prostate (Tramp) model
• Grantee: Valéria Helena Alves Cagnon Quitete
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/03116-4 - Antiangiogenic, finasteride therapies and hormonal response in the prostate microenvironment in the elderly mice
• Grantee: Larissa Akemi Kido de Barros
• Support Opportunities: Scholarships in Brazil - Master