Suppression by nimesulide of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats.
The effects of the cyclooxygenase (COX)-2 inhibitor nimesulide on bombesin-enhanced peritoneal metastasis of azoxymethane (AOM)-induced intestinal adenocarcinomas were investigated in male Wistar rats. From the beginning of the study, the rats were given 10 weekly s.c. injections of AOM (7.4 mg/kg body weight) and s.c. injections of bombesin (40 microg/kg body weight) every other day. From week 16, the rats were given chow pellets containing 200 ppm or 400 ppm nimesulide ad libitum until termination of the study at week 45. Nimesulide at the higher dose significantly decreased the incidence of bombesin-enhanced metastasis to the peritoneum at week 45, although its administration had little or no effect on the location, histologic type, depth of involvement or infiltrating growth patterns of the tumors. Nimesulide also significantly decreased the incidence of bombesin-enhanced lymphatic vessel invasion by adenocarcinomas. Finally, it also inhibited bombesin-induced matrix metalloproteinase (MMP)-9 and pro-MMP-9 inductions. Our findings indicate that nimesulide may inhibit cancer metastasis through inhibition of pro-MMP-9 and MMP-9 inductions.
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. iisi-hi@mc.pref.osaka.jp
Hiroyasu
H
Iishi
Masaharu
M
Tatsuta
Miyako
M
Baba
Hiroyuki
H
Yano
Koji
K
Higashino
Mutsuko
M
Mukai
Hitoshi
H
Akedo
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001397:Azoxymethane / Q000633:toxicity*; D001839:Bombesin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity; D004195:Disease Models, Animal; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology / Q000517:prevention & control; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D013449:Sulfonamides; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D001397:Azoxymethane; D001839:Bombesin; C012655:nimesulide