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Chemoprophylactic effect of celecoxib on N-Methyl-N'-nitro-N-nitrosoguanidine-induced gastric cancer in rat model

JING Da-dao1,LOU Li-hong1,LI En-ling2,LI Ji-kun11.Department of Gastroenterology,Shanghai First People's Hospital,Shanghai JiaotongUniversity,Shanghai 200080,P.R.China2.Shanghai Institute of Digestive Disease,Shanghai 200001,P.R.China  
OBJECTIVE:To investigate the chemoprophylactic effect of celecoxib,a selective cyclooxygenase(COX)-2 inhibitor,on N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-induced gastric cancer in a rat model.METHODS:One hundred and twenty male Wistar rats were randomized to drink the solution of MNNG and high salt food(Group M),MNNG/celecoxib in early stage(Group MCE),MNNG/celecoxib in later stage(Group MCL),celecoxib(Group C),and water(Group N).The animals were assessed for the presence of gastric cancer,COX-2 expression and precancerous changes in gastric mucosa at the and of 35 weeks.RESULTS:One hundred and eleven(92.5%)rats completed the study.The incidences of gastric carcinoma in Group MCE(4.3%)and Group MCL(22.7%)were significantly lower than that in Group M(71.4%),P0.001.No tumor occurred in Group N and Group C.The incidences of gastric mucosal atrophy,intestinal metaplasia and dysplasia in Group MCE were significantly lower than those in Group M(P0.01 and P0.05,respectively).In Group MCL,however,only the incidences of gastric mucosal dysplasia were significantly lower than in Group M,P0.05.The positive rates of COX-2 protein in Group MCE(26.1%)and in Group MCL(45.5%)were also significantly lower than that in Group M(85.7 %),P0.001 and P0.01.CONCLUSIONS:The selective COX-2 inhibitor celecoxib can significantly inhibit the development of gastric cancer and precancerous changes induced by MNNG in the model of rat.This provides an evidence that COX-2 inhibitors may have chemoprophylactic potential in human gastric cancer.
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