title: Role of SMAD4 in the mechanism of valproic acid's inhibitory effect on prostate cancer cell invasiveness.
abstract: OBJECTIVE
  To investigate the influence of the histone deacetylase inhibitor valproic acid (VPA) on SMAD4 expression and invasive ability of prostate cancer cell lines.
  
  
  METHODS
  DU145 and PC3 cell lines were treated with 0, 2, and 5 mMol/l of VPA; invasion of DU145 and PC3 cells were then examined by transwell assay. Immunohistochemistry and Western blot were used to examine SMAD4 protein expression in DU145 and PC3 cells.
  
  
  RESULTS
  Compared with controls, VPA significantly suppressed invasiveness in both PC3 and DU145 cells in a dose-dependent way (P < 0.05). VPA also inhibited AKT protein (which was regarded as an effective indicator here), and meanwhile, SMAD4 expression was down-regulated after VPA treatment in a dose-dependent manner in both DU145 (P < 0.05) and PC3 (P < 0.01) cells.
  
  
  CONCLUSIONS
  Valproic acid could suppress invasiveness of prostate cancer cell lines PC3 and Du145, possibly through multiple pathways other than the SAMD4 pathway. This implies that VPA treatment combined with other SMAD4 enhancers could form a basis for a novel prostate cancer treatment.
authors.affiliation: Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, 250001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Zhongxian
authors.initials: Z
authors.lastname: Huang
authors.forename: Muwen
authors.initials: M
authors.lastname: Wang
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Xunbo
authors.initials: X
authors.lastname: Jin
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Xia
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000473:pathology*; D014176:Protein Biosynthesis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D014635:Valproic Acid; D051057:Proto-Oncogene Proteins c-akt