PMID- 19490185
OWN - NLM
STAT- MEDLINE
DCOM- 20100910
LR  - 20220318
IS  - 1365-2605 (Electronic)
IS  - 0105-6263 (Linking)
VI  - 33
IP  - 3
DP  - 2010 Jun 1
TI  - Combined effect of the finasteride and doxazosin on rat ventral prostate 
      morphology and physiology.
PG  - 489-99
LID - 10.1111/j.1365-2605.2009.00963.x [doi]
AB  - 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-beta1) 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-beta1 
      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-beta1-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.
FAU - Justulin, Luis A Jr
AU  - Justulin LA Jr
AD  - Department of Cell Biology, University of Campinas (UNICAMP), Institute of 
      Biology, Campinas, SP, Brazil.
FAU - Acquaro, Carolina
AU  - Acquaro C
FAU - Carvalho, Robson F
AU  - Carvalho RF
FAU - Silva, Maeli Dal Pai
AU  - Silva MD
FAU - Felisbino, Sergio L
AU  - Felisbino SL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090325
PL  - England
TA  - Int J Androl
JT  - International journal of andrology
JID - 8000141
RN  - 0 (Androgens)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 3XMK78S47O (Testosterone)
RN  - 57GNO57U7G (Finasteride)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - NW1291F1W8 (Doxazosin)
SB  - IM
MH  - Androgens/pharmacology/physiology
MH  - Animals
MH  - Cell Proliferation/drug effects
MH  - Dihydrotestosterone/pharmacology
MH  - Doxazosin/*pharmacology
MH  - Epithelial Cells/cytology/drug effects/physiology
MH  - Extracellular Matrix/chemistry/metabolism/physiology
MH  - Finasteride/administration & dosage/*pharmacology
MH  - Male
MH  - Matrix Metalloproteinase 9/genetics/metabolism/physiology
MH  - Matrix Metalloproteinases/metabolism/pharmacology/physiology
MH  - Prostate/*drug effects/pathology/*physiology
MH  - Prostatic Hyperplasia/pathology
MH  - Prostatic Neoplasms/pathology
MH  - RNA, Messenger/analysis/metabolism/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Testosterone/pharmacology/physiology
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics/pharmacology/physiology
MH  - Tissue Inhibitor of Metalloproteinase-2/genetics/metabolism/physiology
MH  - Transforming Growth Factor beta1/pharmacology/physiology
EDAT- 2009/06/06 09:00
MHDA- 2010/09/11 06:00
CRDT- 2009/06/04 09:00
PHST- 2009/06/04 09:00 [entrez]
PHST- 2009/06/06 09:00 [pubmed]
PHST- 2010/09/11 06:00 [medline]
AID - IJA963 [pii]
AID - 10.1111/j.1365-2605.2009.00963.x [doi]
PST - ppublish
SO  - Int J Androl. 2010 Jun 1;33(3):489-99. doi: 10.1111/j.1365-2605.2009.00963.x. 
      Epub 2009 Mar 25.