Adenocarcina of the mouse prostate growth inhibition by celecoxib: Downregulation of transcription factors involved in COX-2 inhibition

• Published in: The Prostate Vol. 66; no. 3; pp. 257 - 265
• Main Authors: Narayanan, Bhagavathi A., Narayanan, Narayanan K., Pttman, Brian, Reddy, Bandaru S.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-02-2006
• Subjects: adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Animals; Apoptosis - drug effects; Blotting, Western; Celecoxib; Cell Growth Processes - drug effects; COX-2; Cyclooxygenase 2 - metabolism; Cyclooxygenase Inhibitors - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Immunohistochemistry; In Situ Nick-End Labeling; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; NSAIDs; PIN; prostate cancer; Prostatic Intraepithelial Neoplasia - drug therapy; Prostatic Intraepithelial Neoplasia - metabolism; Prostatic Intraepithelial Neoplasia - pathology; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Pyrazoles - pharmacology; Sulfonamides - pharmacology; TRAMP mice; Transcription Factor RelA - antagonists & inhibitors; Transcription Factor RelA - biosynthesis
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20331

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‐κBp65 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. Prostate 9999:1–9,2005. © 2005 Wiley‐Liss, Inc.