Selective cyclooxygenase-2 inhibitor prevents cisplatin-induced tumorigenesis in A/J mice.
Cisplatin is used to treat lung cancer; however, it is also a known carcinogen. Cyclooxygenase-2 (COX-2) inhibitors have been shown to prevent carcinogen-induced experimental tumors. We investigated the effect of a COX-2 inhibitor, celecoxib, on cisplatin-induced lung tumors. One hundred twenty 4-week-old A/J mice were divided into 6 groups: group 1, no treatment; group 2, low-dose celecoxib (150 mg/kg); group 3, high-dose celecoxib (1,500 mg/kg); group 4, cisplatin alone; group 5, cisplatin plus low-dose celecoxib;and group 6, cisplatin plus high-dose celecoxib. Mice in groups 4-6 were administered cisplatin (1.62 mg/kg, i.p.) once a week for 10 weeks between 7 and 16 weeks of age. All mice were sacrificed at week 30. Tumor incidence was 15.8% in group 1, 25% in group 2, 26.3% in group 3, 60% in group 4, 50% in group 5, and 50% in group 6. Tumor multiplicity was 0.2, 0.3, 0.3, 1.3, 1.0, and 0.6 in groups 1-6, respectively. Tumor multiplicity in the cisplatin-treated mice was reduced by celecoxib treatment in a dose-dependent manner (p < 0.05, group 4 vs. group 6). Celecoxib significantly reduced COX-2 expression in cisplatin-induced tumors (p < 0.01, group 4 vs. group 6).
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Toshiaki
T
Okada
Nagio
N
Takigawa
Daizo
D
Kishino
Hideki
H
Katayama
Shouichi
S
Kuyama
Ken
K
Sato
Junko
J
Mimoto
Hiroshi
H
Ueoka
Mitsune
M
Tanimoto
Katsuyuki
K
Kiura
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000068579:Celecoxib; D002945:Cisplatin / Q000633:toxicity*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D002945:Cisplatin