title: Adenocarcina of the mouse prostate growth inhibition by celecoxib: downregulation of transcription factors involved in COX-2 inhibition.
abstract: BACKGROUND
  Epidemiological studies have shown a decreased risk of prostate cancer among men who regularly take aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). In this study, we examined a dose-dependent effect of a cyclooxygenase-2 (COX-2) inhibitor, celecoxib against transgenic adenocarcinoma of the mouse prostate.
  
  
  METHODS
  Efficacy of four different doses in parts per million of celecoxib, such as 200 ppm, 400 ppm, 600 ppm, and 1,000 ppm representing very low, moderate, and high doses, respectively were tested against adenocarcinoma of the mouse prostate using a transgenic adenocarcinoma of the mouse prostate (TRAMP) model assay.
  
  
  RESULTS
  Dietary supplement of celecoxib at doses of 400 ppm, 600 ppm, and 1,000 ppm are most effective against mPIN (mouse prostatic intraepithelial neoplasia) and adenocarcinoma of the prostate. Tumor growth inhibition by celecoxib was associated with increased rate of apoptosis. At 1,000 ppm, a complete inhibition of the PIN lesions was extended to limit the growth of adenocarcinoma (from 85% to 15%) and metastasis of the mouse prostate. The chemopreventive effect was significant (P<0.01) at 400 ppm, 600 ppm, and 1,000 ppm doses compared to that at the lowest dose of 200 ppm and control. A dose-dependent effect on tumor growth inhibition was associated with reduced expression of NF-kappaBp65 and COX-2.
  
  
  CONCLUSIONS
  Dietary supplementation of celecoxib at different doses provides evidence for the suppression of prostate adenocarcinoma tumor growth in a dose-dependent manner. Suppression of adenocarcinoma by celecoxib further limits the growth of metastatic prostate cancer.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA. bhagavathi@env.med.nyu.edu
authors.forename: Bhagavathi A
authors.initials: BA
authors.lastname: Narayanan
authors.forename: Narayanan K
authors.initials: NK
authors.lastname: Narayanan
authors.forename: Brian
authors.initials: B
authors.lastname: Pttman
authors.forename: Bandaru S
authors.initials: BS
authors.lastname: Reddy
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D000068579:Celecoxib; D048708:Cell Growth Processes / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019048:Prostatic Intraepithelial Neoplasia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051996:Transcription Factor RelA; D051546:Cyclooxygenase 2; D000068579:Celecoxib