title: Inhibition of prostate cancer using RNA interference-directed knockdown of platelet-derived growth factor receptor.
abstract: OBJECTIVE
  To determine whether platelet-derived growth factor receptor (PDGFR) plays a role in the tumorigenicity of prostate cancer cells.
  
  
  METHODS
  PC3 prostate cancer cells were transfected with small interfering (si)PDGFR-α and siPDGFR-β, constructed according to the conventional small interfering RNA design standard. Reverse transcriptase polymerase chain reaction, Western blot analysis, and cell growth were studied to determine the characteristics of PDGFR-α and PDGFR-β in vitro. The prostate cancer xenograft model was established to investigate whether knockout of PDGFR-α and PDGFR-β decreases prostate cancer tumor growth in vivo. The experimental groups were defined as group 1 (PC3 cells only), group 2 (PC3 cells transfected with small interfering green fluorescent protein), group 3 (PC3 cells transfected with siPDGFR-α), group 4 (PC3 cells transfected with siPDGFR-β), and group 5 (PC3 cells transfected with siPDGFR-α and siPDGFR-β).
  
  
  RESULTS
  Western blot analysis revealed that siPDGFR-α and siPDGFR-β significantly blocked PDGFR-α and PDGFR-β protein expression. After 48 hours of transfection of the PC3 cells with siPDGFR-α and siPDGFR-β, the relative fractions of viable cells were reduced to 47.7% (P = .007) and 38.5% (P = .010). In vivo, mice treated with siPDGFR-α or siPDGFR-β and siPDGFR-α plus siPDGFR-β had significant tumor cell growth arrest compared with the mice in groups 1 and 2 (P = .001). In addition, a significant reduction in the microvessel density was observed in tumors from the mice treated with siPDGFR-α or siPDGFR-β and siPDGFR-α plus siPDGFR-β (P < .001).
  
  
  CONCLUSIONS
  The results of the present study suggest that siPDGFR-α and siPDGFR-β might inhibit prostate cancer cell growth by the suppression of angiogenesis.
authors.affiliation: Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Park
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Seo
authors.forename: Minju
authors.initials: M
authors.lastname: Ha
authors.forename: Ja Hyeon
authors.initials: JH
authors.lastname: Ku
authors.forename: Hyeon Hoe
authors.initials: HH
authors.lastname: Kim
authors.forename: Cheol
authors.initials: C
authors.lastname: Kwak
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000628:therapy*; D020033:Protein Isoforms; D034622:RNA Interference; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta