Effects of dutasteride on prostate growth in the large probasin-large T antigen mouse model of prostate cancer

J Urol. 2007 Oct;178(4 Pt 1):1521-7. doi: 10.1016/j.juro.2007.05.118. Epub 2007 Aug 16.

Abstract

Purpose: We evaluated the effects of dutasteride for preventing or delaying prostate growth and neoplastic changes in a transgenic model of prostate cancer.

Materials and methods: Large probasin-large T antigen mice were treated for 4 or 8 weeks with dutasteride. The prostate and seminal vesicles were compared with those from intact and castrated large probasin-large T antigen mice and WT mice.

Results: Dutasteride greatly decreased the transgene induced increase in prostate weight but castration caused greater reduction. Dutasteride inhibited type 1 and 2, 5alpha-reductase activities, decreased DNA and protein, and increased apoptotic bodies and TUNEL staining in the dorsolateral prostate. No evidence of poorly differentiated cancer was seen. Dutasteride did not decrease the weight of the androgen dependent levator ani or bulbocavernosus muscle.

Conclusions: Dutasteride inhibited type 1 and 2, 5alpha-reductase activities, and decreased DNA and protein content of the dorsolateral prostate without affecting androgen responsive muscle weight in large probasin-large T antigen mice. These studies provide support for the hypothesis that a 5alpha-reductase inhibitor inhibits the initiation and/or progression of clinical prostate cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • 5-alpha Reductase Inhibitors*
  • Androgen-Binding Protein / genetics*
  • Animals
  • Antigens, Viral, Tumor / genetics*
  • Apoptosis / drug effects
  • Azasteroids / pharmacology*
  • Cell Division / drug effects*
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / pathology
  • Dihydrotestosterone / blood
  • Disease Models, Animal*
  • Dutasteride
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Transgenic
  • Neoplasms, Hormone-Dependent / pathology*
  • Orchiectomy
  • Prostate / drug effects
  • Prostate / pathology
  • Prostatic Hyperplasia / pathology*
  • Prostatic Neoplasms / pathology*
  • Seminal Vesicles / drug effects
  • Seminal Vesicles / pathology
  • Transgenes / genetics*

Substances

  • 5-alpha Reductase Inhibitors
  • Androgen-Binding Protein
  • Antigens, Viral, Tumor
  • Azasteroids
  • Enzyme Inhibitors
  • Membrane Proteins
  • probasin
  • Dihydrotestosterone
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • Srd5a1 protein, mouse
  • Dutasteride