Open AccessChemoprevention by Nimesulide, a Selective Cyclooxygenase‐2 Inhibitor, of 2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐ b ]pyridine (PhIP)‐induced Mammary Gland Carcinogenesis in Rats
Author(s) -
Nakatsugi Seiichi,
Ohta Toshihisa,
Kawamori Toshihiko,
Mutoh Michihiro,
Tanigawa Tetsuya,
Watanabe Kouji,
Sugie Shigeyuki,
Sugimura Takashi,
Wakabayashi Keiji
Publication year - 2000
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2000.tb01030.x
Subject(s) - nimesulide , mammary gland , cyclooxygenase , carcinogenesis , chemistry , anticarcinogen , medicine , endocrinology , cancer , pharmacology , biochemistry , enzyme , breast cancer
Breast cancer is common in women all over the world, and exploration of chemopreventive approaches to this cancer is very important. Nimesulide, a selective inhibitor of cyclooxygenase‐2 (COX‐2), is a good candidate as a chemopreventive agent with low toxicity. We examined its effects on mammary tumor development in female Sprague‐Dawley rats induced with the environmental carcinogen 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐ b ]pyridine (PhIP). Rats at 7 weeks of age received intragastric intubations of PhIP (85 mg/kg body weight) 4 times weekly for 2 weeks and were maintained on control diet (high fat diet) or experimental diet (high fat diet supplemented with 400 ppm nimesulide) throughout the experiment. COX‐2 protein was over‐expressed in epithelial cancer cells and stromal cells of the PhIP‐induced mammary carcinomas, but was weak or not apparent in normal mammary gland cells. The development of mammary carcinomas was clearly suppressed by administration of nimesulide. The carcinoma incidence was 51% as compared to 71% for the control diet group. The average multiplicity of carcinomas in the experimental diet group was 1.2±0.2 ( P < 0.05), significantly smaller than the control diet group value (2.6±0.5). The size of carcinomas was also clearly decreased; 1.1±0.4 cm 3 /rat in experimental diet group ( P < 0.05), 4.1±1.3 cm 3 /rat in the control diet group. The results therefore provide evidence that the selective COX‐2 inhibitor, nimesulide, possesses chemopreventive activity against PhIP‐induced mammary carcinogenesis in rats.