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A selective cyclooxygenase‐2 inhibitor prevents inflammation‐related squamous cell carcinogenesis of the forestomach via duodenogastric reflux in rats
Author(s) -
Oba Masaru,
Miwa Koichi,
Fujimura Takashi,
Harada Shinichi,
Sasaki Shozo,
Oyama Katsunobu,
Ohta Tetsuo,
Hattori Takanori
Publication year - 2009
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23990
Subject(s) - meloxicam , medicine , cyclooxygenase , inflammation , squamous metaplasia , carcinogenesis , gastroenterology , cox 2 inhibitor , celecoxib , epithelium , endocrinology , pathology , enzyme , biology , cancer , biochemistry
BACKGROUND: Duodenal reflux causes inflammation‐related squamous cell carcinogenesis in the forestomach of rats without any carcinogens. The aim of this study was to investigate the efficacy of a selective cyclooxygenase (COX)‐2 inhibitor, meloxicam, in preventing this carcinogenesis. METHODS: A series of 188 rats underwent a surgical duodenogastric reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other was given experimental chow containing meloxicam (0.3 mg/kg body weight/day) (meloxicam group). The animals were sequentially sacrificed at Weeks 20, 30, 40, 50, and 60 after surgery. The forestomach was examined for the presence of carcinoma, the incidence of reflux‐related morphological changes, COX‐2 expression, and its activity. RESULTS: At Week 60, squamous cell carcinoma developed in 8 of 21 animals (38%) in the control group, but none of 20 (0%) in the meloxicam group ( P < .05). In addition, basal cell dysplasia developed in 19 of 21 (90%) animals in the control group, but only 4 of 20 (20%) in the meloxicam group ( P < .01). COX‐2 immunoreactivity was predominantly detected in macrophages in the epithelial stroma. Compared with nonsurgical rats, RNA expression of COX‐2 in the epithelium was up‐regulated, reaching peak at an early stage of Week 20 in both groups ( P < .005). The expression of microsomal prostaglandin E synthase‐1 was lower in the meloxicam group than in the control group. PGE 2 production was significantly suppressed throughout the experiment in the meloxicam group compared with the control group ( P < .005). CONCLUSIONS: Meloxicam was effective in preventing reflux‐induced squamous cell carcinogenesis via an inflamed squamous epithelium. Cancer 2009. © 2009 American Cancer Society.