Effect of 1, 25-Dihydroxyvitamin D_3 on Gastric Carcinogenesis Induced by N-Methyl-N'-nitro-N-nitrosoguanidine in Rats

The effect of 1, 25-dihydroxyvitamin D3 (1, 25 (OH)2D3) given in the post-initiation stage of gastric carcinogenesis induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was investigated in male Wistar rats. Gastric carcinogenesis in rats was induced by administration of MNNG (150 mg·L-1) in drinking water. Four weeks after MNNG exposure, the rats were switched to the diet containing 1, 25 (OH)2D3 (2. 5 μg·kg-1 and 5. 0 μg·kg-1) and maintained on the diet. Animals were killed at week 16 and week 32 for immunohistochemical and histopathological studies. At week 16, the proliferating cell nuclear antingen (PCNA) labeling index in epithelium from the glandular stomach of rats that received 1, 25 (OH)2D3 (5.0 μg·kg-1) in combination with MNNG (150 mg·L-1) were significantly higher when compared with the rats receiving MNNG alone. Supplementation of 1, 25 (OH)2D3 (5. 0 μg·kg-1) in the rats' diet caused a dramatic increase in carcinoma incidence, and the number of individual cancer foci in the glandular stomach of rats receiving MNNG at week 32. It was concluded that certain dose of 1, 25 (OH)2D3 enhanced gastric carcinogenesis induced by MNNG in rats.

INHIBITORY EFFECT OF GLYCYRRHIZA URALENSIS FISH AND CHELIDONIUM MAJUS L ON GASTROCARCINOGENESIS . INDUCED BY N-METHYL-N' -NITRO-N-NITROSOGUANIDINE

In order to investigate the antagonistic effect of Glycyrrhlza Uralensis Fish (GUF) and Chelidonium maJus L (CML) on gastrccarcinogenesls Induced by MNNG in Wastar rats, we treated the rats with MNNG alone (group 1) and with MNNG plus GUF and CML (group 2 and 3) respectively. The Incidence of Infiltrating adenocarcinoma of the glandular stomach and duodenum in group 2 was significantly lower than that in group 1 (26.7% vs. 67.8%). The differentiation and aggresslvenees of carcinomas occured in group 2 were much better and mild than those in group 1. Present study also demonstrated that the Inhibitory effect of CML on proliferation of human stomach carcinoma cell line MGC-803 was very remarkable; in addition, GUF and CML were able to antagonise the mutagenlc activation of MNNG. These results suggest that GUF and CML may be empoyed In prevention of gastric carcinoma.

Expression of p-STAT3 and vascular endothelial growth factor in MNNG-induced precancerous lesions and gastric tumors in rats

AIM: To investigate the dynamic expression of p-signal transducer and activator of transcription 3(STAT3) and vascular endothelial growth factor(VEGF) in the formation of gastric tumors induced by drinking water containing N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) in Wistar rats.METHODS: One hundred and twenty Wistar rats were randomly divided into two groups(60 in each group): Control group and Model group. The rats in each group were then randomly divided into three groups(20 in each group): C/M15, C/M25 and C/M40(15, 25 and 40 represent the number of feeding weeks from termination). Rats in the control group received normal drinking water and rats in the model group received drinking water containing 100 μg/m L MNNG. Stomach tissues were collected at the end of the 15 th, 25 th and 40 th week, respectively, for microscopic measurement using hematoxylin and eosin staining. The expression of p-STAT3 and VEGF in different pathological types of gastric tissue, including normal, inflammation, atrophy, hyperplasia and gastric stromal tumor, was observed by immunohistochemistry and Western blot, and the corelation between p-STAT3 and VEGF was analyzed. RESULTS:(1) The expression of p-STAT3 in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor were significantly increased in the model group compared with the control group(2.5 ± 1.0, 2.75 ±0.36, 6.2 ± 0.45, 5.67 ± 0.55 vs 0.75 ± 0.36, P = 0.026, 0.035, 0.001, 0.002, respectively); the expression of p-STAT3 in tissue with dysplasia was higher than that in samples with gastritis or atrophy(6.2 ± 0.45 vs 2.5 ± 1.0, P = 0.006; 6.2 ± 0.45 vs 2.75 ± 0.36, P = 0.005, respectively); however, the expression of p-STAT3 in gastritis and atrophy was not significantly different(P > 0.05);(2) the expression of VEGF in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor was significantly increased in the model group compared with normal gastric mucosa; and the expression of VEGF in tissue with dysplasia was higher than that in tissue with inflammation and atrophy(10.8 ± 1.96 vs 7.62 ± 0.25, P = 0.029; 10.8 ± 1.96 vs 6.26 ± 0.76, P = 0.033, respectively); similarly, the expression of VEGF in tissue with gastritis and atrophy was not significantly different(P > 0.05); and(3) the expression of VEGF was positively correlated with p-STAT3. CONCLUSION: p-STAT3 plays an important role in gastric cancer formation by regulating the expression of VEGF to promote the progression of gastric tumor from gastritis.