塞莱西布对甲基硝基亚硝基胍诱导大鼠胃癌的化学预防作用

目的：探讨选择性环氧合酶-2（COX-2）抑制剂塞莱西布对N-甲基-N′-硝基-M亚硝基胍（MNNG）诱发大鼠胃癌的化学预防作用。方法：将120只雄性Wistar大鼠分成5组分别予以不同饮食及药物：胃癌模型组（M组，给予MNNG和高盐饮食）、塞莱西布早期干预组（MCE组）和晚期干预组（MCL组）、塞莱西布对照组（C组）和正常对照组（N组，纯净水）。喂养35周后观察各组大鼠的胃黏膜病变及胃癌形成情况。结果：111（92．5％）只大鼠完成实验。MCE组和MCL组大鼠胃癌发生率分别为4．3％和22．7％，均显著低于M组（71．4％，P〈0．001和〈0．010）；N组和C组均无胃癌发生。MCE组大鼠胃黏膜萎缩、肠化生和异型增生的发生率显著低于M组，P〈0．01；MCL组大鼠胃黏膜异型增生发生率亦显著低于M组，P〈0．05，但其萎缩和肠化生的发生率与M组之间无统计学意义。MCE组和MCL组大鼠胃黏膜COX-2蛋白表达的阳性率分别为26．1％和45．5％，亦显著低于M组（85．7％，P〈0．001和P〈O．01）。结论：选择性COX-2抑制剂塞莱西布能有效抑制MNNG诱导的大鼠胃癌及癌前病变的发生，这为C0X-2抑制剂对人类胃癌进行化学预防和治疗提供了实验证据。

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

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%),P<0.001.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(P<0.01 and P<0.05,respectively).In Group MCL,however,only the incidences of gastric mucosal dysplasia were significantly lower than in Group M,P<0.05.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 %),P<0.001 and P<0.01.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.