A selective cyclooxygenase-2 inhibitor prevents inflammation-related squamous cell carcinogenesis of the forestomach via duodenogastric reflux in rats.
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. PGE2 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.
Oba
Masaru
M
Gastroenterological Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Miwa
Koichi
K
Fujimura
Takashi
T
Harada
Shinichi
S
Sasaki
Shozo
S
Oyama
Katsunobu
K
Ohta
Tetsuo
T
Hattori
Takanori
T
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004383:Duodenogastric Reflux / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000517:prevention & control*; D008297:Male; D000077239:Meloxicam; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013274:Stomach Neoplasms / Q000209:etiology / Q000517:prevention & control*; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D000077239:Meloxicam