Antiangiogenic, Finasteride therapies and hormonal response in the prostate microenvironment in the elderly mice

Author(s)

Larissa Akemi Kido

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2013-02-15

Examining board members

Valéria Helena Alves Cagnon; Carlos Alberto Vicentini; Débora Barbosa Vendramini Costa

• Advisor: Valéria Helena Alves Cagnon

Abstract

Senescence is associated with significant changes in the hormonal environment and is a cause of morphological and functional changes in the prostate. The different biological processes that occur in the prostate are influenced by different factors such as vascular endothelial growth factor (VEGF) and Endostatin, related to angiogenesis. Also, 5_-reductase inhibitors, such as finasteride, play an important role in treatment of prostatic diseases. Thus, the aims of this study were to evaluate the structural and molecular effects of antiangiogenic therapies and finasteride on the ventral prostate of mice during senescence. Ninety 52 and 18 week old male FVB mice, were divided into groups: Young (YNG) and Senile (SEN) groups, which received 0.9% saline (5 mL/kg/day sc) injections; Finasteride (FIN) group: Finasteride (20 mg/kg, sc); SU5416 (SU) group: SU5416 (6 mg/kg, ip) injections; TNP-470 (TNP) group: TNP-470 (15 mg/kg, sc) injections and SU5416+TNP-470 (SU+TNP470) group: The same treatment as the SU and TNP-470 groups. After 21 days of treatment, samples of the ventral lobe of the prostate were collected and analyzed for morphological, immunohistochemical and Western Blotting analyses. The results demonstrated structural and molecular changes in the prostatic microenvironment during senescence, such as atrophy, inflammatory cells, and proliferative lesions, which were interrupted and/or blocked by treatment with antiangiogenic drugs and finasteride. The molecular results revealed decreased reactivity for AR and Endostatin, and an increase for ER-_, ER-_ and VEGF in the senile group, when compared to young mice. The mice in the groups treated with finasteride, SU5416 and SU5416 + TNP-470, when compared to the senile group, showed in general decreased VEGF and ER-_ reactivities and increased ER-_ reactivity. The treatment with TNP-470 however, was marked mainly by reduced AR and ER-_ reactivity and protein levels, when compared to young and senile groups. Thus, it can be concluded that senescence contributed to the occurrence of structural and/or molecular alterations that suggest the onset of malignant lesions, due to the imbalance in the signaling between the epithelium and stroma. Treatments with finasteride, SU5416 and SU5416+TNP-470, were active in the regulation of proliferative processes by means of the estrogen pathways (AU)

• 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