Increased expression of cyclooxygenase (COX)-2 in DMBA-induced hamster cheek pouch carcinogenesis and chemopreventive effect of a selective COX-2 inhibitor celecoxib.
BACKGROUND
In recent years, overexpression of cyclooxygenase (COX)-2 protein and mRNA has been reported in various cancer tissues. Therefore, it has been suggested that COX-2 is related to carcinogenesis.


METHODS
Hamsters were treated by painting a buccal pouch with a 0.5% DMBA solution dissolved in acetone. Basal diet or diets containing 150, 500 and 1500 ppm of celecoxib, a selective COX-2 inhibitor, were given ad libitum to hamsters, and tumor development was observed.


RESULTS
Immunohistochemical and Western blot analyses revealed that COX-2 expression was increased toward the carcinogenesis. Although all hamsters developed squamous cell carcinoma, the onset of tumor formation was delayed in a dose-dependent manner. Also, tumor growth was retarded and survived animals were increased in the group of celecoxib treatment. Histologically, administration of celecoxib increased the apoptotic cells in the tumor parenchyma and significantly inhibited the angiogenesis in the stroma.


CONCLUSIONS
The COX-2 expression was increased during hamster cheek pouch chemical carcinogenesis. Administration of celecoxib demonstrated the chemopreventive potential against the carcinogenesis.
Nishimura
Norihiko
N
Department of Oral and Maxillofacial Surgery, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Urade
Masahiro
M
Hashitani
Susumu
S
Noguchi
Kazuma
K
Manno
Yukiyo
Y
Takaoka
Kazuki
K
Sakurai
Kazunari
K
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control; D000068579:Celecoxib; D002610:Cheek; D006224:Cricetinae; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008297:Male; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011720:Pyrazoles; D013449:Sulfonamides / Q000008:administration & dosage*
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