title: The effect of cyclooxygenase-2 (COX-2) inhibition on human prostate cancer induced osteoblastic and osteolytic lesions in bone.
abstract: BACKGROUND
  The mechanism of bone formation by osteoblastic prostate cancer metastases is not well defined. Using knockout mice, it has been demonstrated that prostaglandins produced by COX-2 are critical for fracture repair. Therefore, our aim was to determine if COX-2 plays a role in the bone formation in osteoblastic prostate cancer metastases in bone.
  
  
  METHODS
  We assessed the influence of pharmacologic COX-2 inhibition in a SCID mouse intratibial injection model of bone metastasis using two human prostate cancer cell lines that produce either osteoblastic lesions (LAPC-9) or osteolytic lesions (PC-3, negative control). SC-58236, a COX-2 specific inhibitor, was used at a dose of 3 mg/Kg intraperitoneally 3 times per week in the Treatment groups for 8 weeks until sacrifice.
  
  
  RESULTS
  Western blot for COX-2 demonstrated that LAPC-9 cells expressed high levels of COX-2 while PC-3 cells did not. Treatment with SC-58236 significantly reduced the size of osteoblastic lesions after LAPC-9 injection based on both radiographic and histomorphometric criteria compared to the control group. In contrast, large osteolytic lesions were seen in both control and SC-58236 treated animals after PC-3 cell injections. The results of this study indicate that COX-2 inhibition can decrease the size of osteoblastic lesions produced by LAPC-9, a human prostate cancer cell line that expresses high levels of COX-2. This treatment had no effect on the osteolytic activity of PC-3 cells.
  
  
  CONCLUSIONS
  These findings suggest that the progression of osteoblastic metastases induced by human prostate cancer cells may be limited by COX-2 inhibitors.
authors.affiliation: Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Seth C
authors.initials: SC
authors.lastname: Gamradt
authors.forename: Brian T
authors.initials: BT
authors.lastname: Feeley
authors.forename: Nancy Q
authors.initials: NQ
authors.lastname: Liu
authors.forename: Jason
authors.initials: J
authors.lastname: Roostaeian
authors.forename: Ying Q
authors.initials: YQ
authors.lastname: Lin
authors.forename: Li X
authors.initials: LX
authors.lastname: Zhu
authors.forename: Sherven
authors.initials: S
authors.lastname: Sharma
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dubinett
authors.forename: Jay R
authors.initials: JR
authors.lastname: Lieberman
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000556:secondary*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D016513:Mice, SCID; D010006:Osteoblasts / Q000201:enzymology / Q000473:pathology; D010014:Osteolysis / Q000201:enzymology / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C496540:PTGS2 protein, human