JTE-522, a selective COX-2 inhibitor, inhibits growth of pulmonary metastases of colorectal cancer in rats.
BACKGROUND
Epidemiological studies have shown that individuals who regularly consume NSAIDs have lower rates of mortality associated with colorectal cancer. Because COX-2 inhibitors prevent tumor growth through some mechanisms, we assessed the effect of JTE-522, a selective COX-2 inhibitor, on pulmonary metastases of colon cancer in a rat model.


METHODS
A suspension of 5 x 10(6) RCN-9 (rat colon cancer cells) was injected into the tail vein of 24 anesthetized male F344/DuCrj rats. Oral JTE-522 (0, 3, 10, or 30 mg/kg/day) was administered from the day before RCN-9 injection until the end of the study. Twenty-four days later, the lungs were removed from sacrificed rats and weighed. Pulmonary metastatic tumors were microscopically evaluated in the largest cross sections. We also performed immunohistochemical staining for both COX-2 and VEGF.


RESULTS
JTE-522 dose-dependently decreased lung weight (p = 0.001) and the size of pulmonary metastatic tumors (p = 0.0002). However, the differences in the number of metastatic tumors among 4 groups were insignificant. Significant adverse effects of JTE-522 were undetectable. Immunohistochemical staining showed high levels of both COX-2 and VEGF in pulmonary metastatic tumors.


CONCLUSIONS
JTE-522 dose-dependently decreased the size, but not the number of pulmonary metastases. COX-2 inhibitors might block metastatic tumor growth, but not actual metastasis. Selective COX-2 inhibitors might be useful as therapeutic agents that inhibit the growth of metastatic tumors, as well as the tumorigenesis of colorectal cancer.
Kobayashi
Hirotoshi
H
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. koba@ndmc.ac.jp
Uetake
Hiroyuki
H
Higuchi
Tetsuro
T
Enomoto
Masayuki
M
Sugihara
Kenichi
K
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D009929:Organ Size / Q000187:drug effects; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D000096926:Benzenesulfonamides
D001557:Benzenesulfonates; D052246:Cyclooxygenase 2 Inhibitors; D010080:Oxazoles; D042461:Vascular Endothelial Growth Factor A; C110453:4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; D000096926:Benzenesulfonamides
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