title: Finasteride inhibits human prostate cancer cell invasion through MMP2 and MMP9 downregulation.
abstract: BACKGROUND
  The use of the 5-alpha reductase inhibitors (5-ARIs) finasteride and dutasteride for prostate cancer prevention is still under debate. The FDA recently concluded that the increased prevalence of high-grade tumors among 5-ARI-treated patients must not be neglected, and they decided to disallow the use of 5-ARIs for prostate cancer prevention. This study was conducted to verify the effects of finasteride on prostate cell migration and invasion and the related enzymes/proteins in normal human and tumoral prostatic cell lines.
  
  
  METHODS
  RWPE-1, LNCaP, PC3 and DU145 cells were cultivated to 60% confluence and exposed for different periods to either 10 µM or 50 µM finasteride that was diluted in culture medium. The conditioned media were collected and concentrated, and MMP2 and MMP9 activities and TIMP-1 and TIMP-2 protein expression were determined. Cell viability, migration and invasion were analyzed, and the remaining cell extracts were submitted to androgen receptor (AR) detection by western blotting techniques. Experiments were carried out in triplicate.
  
  
  RESULTS
  Cell viability was not significantly affected by finasteride exposure. Finasteride significantly downregulated MMP2 and MMP9 activities in RWPE-1 and PC3 cells and MMP2 in DU145 cells. TIMP-2 expression in RWPE-1 cells was upregulated after exposure. The cell invasion of all four tested cell lines was inhibited by exposure to 50 µM of finasteride, and migration inhibition only occurred for RWPE-1 and LNCaP cells. AR was expressed by LNCaP, RWPE-1 and PC3 cells.
  
  
  CONCLUSIONS
  Although the debate on the higher incidence of high-grade prostate cancer among 5-ARI-treated patients remains, our findings indicate that finasteride may attenuate tumor aggressiveness and invasion, which could vary depending on the androgen responsiveness of a patient's prostate cells.
authors.affiliation: Univ Estadual Paulista - UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Lab, Botucatu, São Paulo, Brazil ; Univ Estadual Paulista - UNESP, Botucatu Medical School, Blood Transfusion Center, Cell Engineering Lab, Botucatu, São Paulo, Brazil.
authors.forename: Andrei
authors.initials: A
authors.lastname: Moroz
authors.affiliation: Univ Estadual Paulista - UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Lab, Botucatu, São Paulo, Brazil.
authors.forename: Flávia K
authors.initials: FK
authors.lastname: Delella
authors.affiliation: Univ Estadual Paulista - UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Lab, Botucatu, São Paulo, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Almeida
authors.affiliation: Univ Estadual Paulista - UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Lab, Botucatu, São Paulo, Brazil ; Univ Campinas - UNICAMP, Institute of Biology, Department of Structural and Functional Biology, Campinas, São Paulo, Brazil.
authors.forename: Lívia Maria
authors.initials: LM
authors.lastname: Lacorte
authors.affiliation: Univ Campinas - UNICAMP, Institute of Biology, Department of Structural and Functional Biology, Campinas, São Paulo, Brazil.
authors.forename: Wágner José
authors.initials: WJ
authors.lastname: Fávaro
authors.affiliation: Univ Estadual Paulista - UNESP, Botucatu Medical School, Blood Transfusion Center, Cell Engineering Lab, Botucatu, São Paulo, Brazil ; Univ Estadual Paulista - UNESP, Botucatu Medical School, Department of Urology, Botucatu, São Paulo, Brazil.
authors.forename: Elenice
authors.initials: E
authors.lastname: Deffune
authors.affiliation: Univ Estadual Paulista - UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Lab, Botucatu, São Paulo, Brazil.
authors.forename: Sérgio L
authors.initials: SL
authors.lastname: Felisbino
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D018120:Finasteride / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D058891:5-alpha Reductase Inhibitors; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011991:Receptors, Virus; D019716:Tissue Inhibitor of Metalloproteinase-2; D018120:Finasteride; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9