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

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

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-N-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<0.01)。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COX-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。

To investigate the chemoprophylactic effect of celecoxib, a selective cyclooxygenase （COX）-2 inhibi- tor, 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.