Combined effect of the finasteride and doxazosin on rat ventral prostate morphology and physiology

Autor(es)

Justulin, Jr., Luis A. ^[1] ; Acquaro, Carolina ^[2] ; Carvalho, Robson F. ^[2] ; Silva, Maeli Dal Pai ^[2] ; Felisbino, Sergio L. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Dept Cell Biol, Inst Biol, Campinas, SP - Brazil

^[2] UNESP, Dept Morphol, Inst Biosci, Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF ANDROLOGY; v. 33, n. 3, p. 489-499, JUN 2010.
• Citações Web of Science: 14

Resumo

P>Finasteride (Fin) and Doxazosin (Dox), alone or in combination, have been widely used in treatment of benign prostatic hyperplasia (BPH) symptoms and recently have been suggested as potential drugs for prostate cancer (PCa)prevention and treatment. However, little is known about the effects of the combination therapy on prostate tissue morphology, physiology and matrix metalloproteinases (MMPs) activity, a special set of enzymes closely related to PCa progression and metastasis. In this study, adult Wistar rats were treated with Fin + Dox (25 mg/kg per day) and the ventral prostate (VP) was excised at days 3 and 30 of treatment to evaluate morphology, cell proliferation, death, transforming growth factor-beta1 (TGF-beta 1) protein expression, MMP-2, MMP-9 activities and MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA expression. Fin + Dox treatment induced a transient increase in testosterone (T) plasma concentration and a permanent reduction in dihydrotestosterone (DHT). The VP and epithelial cell proliferation were reduced and the stromal collagen fibre volume fraction and apoptosis of the epithelial cell were increased. Fin + Dox treatment also increased the TGF-beta 1 immunoreaction in the epithelium and in the stroma. The mRNAs for MMP-2, TIMPs-1 and -2 expressions after 30 days of treatment were decreased. The mRNA for MMP-9 was not detected in any of the groups analysed. Fin + Dox treatment for 30 days promoted a decrease in gelatinolytic activity of MMP-2 and an increase in MMP-9. In conclusion, combined treatment with Fin and Dox interferes in the epithelial cell behaviour and in the MMPs activity, potentially via TGF-beta 1-mediated and androgen pathways. Our results contribute to a better understanding of the clinical data and also of the molecular mechanisms behind isolated or combined Fin and Dox long-term treatment. (AU)

• Processo FAPESP: 04/13261-8 - Efeito da doxazosina e da finasterida sobre a interação epitélio-estroma nos diferentes lóbulos da próstata de rato: proliferação e morte celular e atividade de metaloproteinases de matriz
• Beneficiário: Sérgio Luis Felisbino
• Modalidade de apoio: Auxílio à Pesquisa - Regular