Antiangiogenic and chemopreventive activities of celecoxib in oral carcinoma cell.
OBJECTIVE
Chemoprevention is a promising strategy to inhibit carcinoma before invasive tumors develop, but a new molecular target is desirable. Celecoxib is a newly developed cyclo-oxygenase (COX)-2 inhibitor with significantly less toxicity. The study was conducted to determine whether celecoxib is effective and safe in prevention of oral cancer. The antiangiogenic activity of celecoxib was studied to explore the potential mechanism involved.


METHODS
Randomized animal study.


METHODS
The study consisted of two phases. In the phase 1,10 mice were used to determine the efficacy and safety of celecoxib with intradermal inoculation with oral carcinoma cells. The 10 mice were equally divided into two groups 5 mice (30 inoculated sites) in each group to receive 1,500 parts per million (ppm) celecoxib mixed in with the diet or to eat a normal diet, respectively, for 21 days. In phase 2, 10 more mice were inoculated to determine the effect of celecoxib on angiogenesis. Five mice received 3,000 ppm celecoxib in the diet, with the other five mice as control animals. The antiangiogenic activity was evaluated by comparing the density of newly growing microvessels after the inoculation.


RESULTS
The results indicated that celecoxib significantly delayed cell growth and reduced tumor volume. There was statistical significance in the quantity of new vasculature in the tumor sites between the two groups. No toxic effect was found by means of measurement of body weight loss and microscopic dissection of organs.


CONCLUSIONS
The study provided the first evidence to show the chemopreventive efficacy of celecoxib on oral cancer in a nude mouse model. Clinical trials are warranted to determine the efficacy in humans.
Wang
Zhi
Z
Department of Otolaryngology-Head and Neck Surgery and Otolaryngology Research Center, New England Medical Center, Boston, Massachusetts, USA. zwang@bu.edu
Fuentes
Cesar F
CF
Shapshay
Stanley M
SM
D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000473:pathology / Q000517:prevention & control*; D000068579:Celecoxib; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007624:KB Cells / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000098:blood supply / Q000473:pathology / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib