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

Autor(es)

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

Afiliação do(s) autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 106, n. 1-2, p. 58-70, JUN 13 2014.
• Citações Web of Science: 4

Resumo

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)

• Processo FAPESP: 12/03010-4 - Caracaterização molecular da próstata frente às terapias hormonais e antiangiogênicas em camundongos senis (FVB) e no modelo transgênicos (Tramp) para adenocarcinoma de próstata
• Beneficiário: Valéria Helena Alves Cagnon Quitete
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/03116-4 - Terapias antiangiogênicas, uso de finasterida e resposta hormonal na senilidade na próstata de camundongos
• Beneficiário: Larissa Akemi Kido de Barros
• Modalidade de apoio: Bolsas no Brasil - Mestrado