Chemoprevention of breast cancer in rats by celecoxib, a cyclooxygenase 2 inhibitor.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been observed to reduce the relative risk of breast cancer. This prompted our investigation of the chemopreventive potential of celecoxib, a specific cyclooxygenase 2 blocker, against mammary carcinogenesis induced by 7,12-dimethyl-benz(a)anthracene in female Sprague Dawley rats. Treatment with celecoxib was examined and compared to treatment with the general NSAID, ibuprofen, and to a control group receiving only dimethylbenz(a)anthracene. Dietary administration of celecoxib (1500 ppm) produced striking reductions in the incidence, multiplicity, and volume of breast tumors relative to the control group (68%, 86%, and 81%, respectively; P < 0.001). Ibuprofen also produced significant effects, but of lesser magnitude (40%, 52%, and 57%, respectively; P < 0.001). These results help confirm the chemopreventive activity of NSAIDs against breast cancer and provide the first evidence that a cyclooxygenase 2 blocking agent, celecoxib, possesses strong chemopreventive activity against mammary carcinogenesis.
Harris
R E
RE
School of Public Health, The Ohio State University College of Medicine, Columbus 43210, USA.
Alshafie
G A
GA
Abou-Issa
H
H
Seibert
K
K
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D007052:Ibuprofen / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D007527:Isoenzymes / Q000378:metabolism / Q000494:pharmacology*; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology* / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000494:pharmacology*; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity; D013449:Sulfonamides / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D015127:9,10-Dimethyl-1,2-benzanthracene; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D007052:Ibuprofen