Chemopreventive effect of oxymatrine on N-methyl-N′-nitro-N-nitrosoguanidine induced gastrointestinal cancer:experiment with rats

Objective To investigate the chemopreventive effect of oxymatrine on the N-methyl-N- nitrn-N-nitrosoguanidine(MNNG)-induced gastrointestinal cancer.Methods Ninety-nine male Wistar rats were randomly allocated into four groups:MNNG treated group(36 rats,fed with MNNG for 28 weeks so as to establish rat model of gastrointestinal cancer),oxymatrine intervention group(n=23,fed with MNNG and oxymatrine),negative control group(20 rats,fed with mixed feed),and oxymatrine control group (20 rats.fed with normal food and oxymatrine).28 weeks later all the rats began to be fed with normal food for 4 weeks,two rats in the MNNG treated group were killed at the 28 th,32 nd,and 40 th weeks of the experiment respectively to observe the tumor growth in the gastrointestinal tract.At the 44 th week all the rats were sacrificed and assessed for the presence of gastrointestinal tumor.Immunohistochemistry was used to detect the expression of Ki67,an antigen associated to the proliferation of nucleus.The cell apoptosis rate in the tumor tissue was detected by TUNEL method.Results Experiment was completed in 92 rats (92.93%).The incidence of gastrointestinal tumor in the MNNG treated group was 58.62%(17/29), significantly higher than that in the oxymatrine treated group(30.43 %,7/23,P0.05).Duodenum tumor was found in 1 rat of the negative control group and no tumor was found in the oxymatrine control group.The average volume of tumor in the MNNG treated group was 2.56(full range 49.5)em~3,significantly larger than those of the oxymatrine treated group[0.03(full range 0.009)cm~3],and negative control group(0.5cm~3 ) (both P0.05).The incidence rates of gastrointestinal mueosal ulceration and dysplasia of the MNNG treated group were higher than those of the oxymatrine treated group(both P0.05).The expression rate of Ki67 in the tumor tissue of the MNNG treated group was(48±18)%,significantly higher than that of the oxymatrine treated group[(25±24) %,P0.05].The apoptotic rate of tumor cell in the MNNG treated group was(11±7)%,significantly lower than that in the oxymatrine treated group[(30±16)%,P= 0.002].Conclusion Inhibiting the development and inducing the apoptosis of gastrointestinal tumor induced by MNNG,oxymatrine can be used as a chemopreventive agent against gastrointestinal tumor.