title: Survivin is associated with cell proliferation and has a role in 1a,25-dihydroxyvitamin D3 induced cell growth inhibition in prostate cancer.
abstract: OBJECTIVE
  Prostate cancer cell proliferation is inhibited by 1a,25-dihydroxyvitamin D(3). Survivin is a member of the inhibitors of apoptosis protein family. Several studies indicate that survivin down-regulation sensitizes human tumor cells of different histological origins to conventional chemotherapeutic drugs. We assessed the effect of survivin gene expression on the proliferation of prostate cancer cells in vitro and in vivo. We also examined the antitumor sensitization effect of survivin inhibition in 1a,25-dihydroxyvitamin D(3) treatment for prostate cancer cells.
  
  
  METHODS
  We knocked down gene expression levels of survivin using siRNA against survivin in vitro and in vivo. We then assessed survivin expression in 1a,25-dihydroxyvitamin D(3) treatment and examined the antitumor sensitization effect of survivin inhibition using siRNA in 1a,25-dihydroxyvitamin D(3) treatment of hormone resistant prostate cancer cells.
  
  
  RESULTS
  In vitro and in vivo siRNA against survivin significantly inhibited cell and tumor growth compared with control siRNA. In LNCaP and PC3 cells 1a,25-dihydroxyvitamin D(3) decreased survivin gene expression and inhibited cell proliferation. However, survivin gene expression and cell proliferation were not inhibited in DU145 cells but after siRNA transfection against survivin DU145 cell proliferation was inhibited by 1a,25-dihydroxyvitamin D(3).
  
  
  CONCLUSIONS
  Findings suggest that survivin has a significant association with prostate cancer cell proliferation and an essential role in 1a,25-dihydroxyvitamin D(3) induced prostate cancer cell growth inhibition. It seems that the eliminating survivin in 1a,25-dihydroxyvitamin D(3) therapy for hormone refractory prostate cancer is a potential therapeutic option.
authors.affiliation: Department of Urology, Gunma University Graduate School of Medicine, Gunma, Japan. hkoike@med.gunma-u.ac.jp
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Koike
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekine
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsui
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shibata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000517:prevention & control*; D000077022:Survivin; D014407:Tumor Cells, Cultured
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D002117:Calcitriol