| Objective: To study the effect of epigallocatechin gallate(EGCG)on colorectal tumor induced by azoxymethane(AOM)/dextran sulfate sodium(DSS)in mice and explore its role in influencing tumorigenesis.Methods: Thirty female young BALB/c mice were randomly divided into control group,AOM/DSS group,and AOM/DSS+EGCG group(n=10 in each group).At the beginning of the experiment,mice in the AOM+DSS group and the AOM+DSS+EGCG group were intraperitoneally injected with 0.1% AOM(10mg/kg),and the control group was intraperitoneally injected with normal saline(10mg/kg)and recorded the initial weight of the three groups of mice.Normal water was kept for 1 week.At the 2nd week,AOM+DSS group and AOM+DSS+EGCG group were given 2% DSS solution.At the 3rd and 4th week,AOM+DSS+EGCG group was given 0.01% EGCG solution and the AOM+DSS group was fed with normal water.The AOM+DSS group received 1 week of DSS and 2 weeks of normal water for one cycle,and the AOM+DSS+EGCG group received 1 week of DSS and 2 weeks of EGCG for one cycle.After repeated for 3 cycles,each group was fed with ordinary water for 3 weeks.The control group was fed with normal water all the time.The body weight,mental status and defecation of mice in each group were observed and recorded every week.The weight of mice were recorded every week and the mice were killed after 13 weeks.The incidence rate of colorectal tumors and the number of tumors in each group were recorded.Mouse colorectal tissue or tumor tissue was subjected to HE staining and were diagnosed by pathologist.The immunohistochemical method was used to detect the CD31-labeled microvessel density(MVD)and the number of CD68-labeled CD68+ macrophages in colorectal tumor tissues of tumor-bearing mice.Results:The body weight of the mice was measured weekly after the start of the experiment.The weight of the mice in the control group increased steadily.The weight gain of the AOM/DSS group and the AOM/DSS+EGCG group was slower,meanwhile,the weight loss occurred during the experiment in AOM/DSS group and the AOM/DSS+EGCG group.At the end of the experiment,the average body weight of the AOM/DSS group(21.45±1.11g)was lighter than that of the control group(22.63±1.04g)(P < 0.05);the average of the AOM/DSS+EGCG mice at the end of the experiment was 20.98±0.95 g,which was significantly different from the control group(P <0.01),but there was no significant difference compared with the AOM/DSS group(P > 0.05).The colorectal tissues of all mice were dissected.The color of the colorectal surface of the control mice was ruddy,no ulcer,and no tumor formation.Four mice in the AOM/DSS group showed tumors in the colorectal;one mouse of AOM/DSS+EGCG group died in the initial stage of the experiment,and four mice in the remaining mice showed tumors in the colorectal.According to the number of tumors,the number of tumors of AOM/DSS+EGCG group was significantly higher than that of AOM/DSS tumor group(P<0.05).The results of HE staining showed that there was no dysplasia of colorectal tissue in the control group.Two cases of low-grade intraepithelial neoplasia,two cases of high-grade intraepithelial neoplasia and six cases of no tumor lesions in the AOM/DSS group.The tumor incidence of AOM/DSS group(40%,4/10)was statistically significant compared with the control group(P<0.05).One case of low-grade intraepithelial neoplasia,and three cases of high-grade intraepithelial neoplasia and five cases of no tumor lesions in the AOM/DSS+EGCG group,and the tumor incidence(44.44%,4/9)was statistically significant compared with the control group(P<0.05),but there was no significant difference compared with AOM/DSS group(P>0.05).The colorectal gland structure of the mice in control group was normal and no atrophy.Crypt destruction,mucosal surface ulcer and neutrophil infiltration were observed in colorectal tumor tissues of mice in AOM/DSS group.In addition to inflammatory cell infiltration,colorectal tumor tissues of mice in AOM/DSS+EGCG group were observed to have atrophy of the intrinsic glands,large cell staining,irregular shape,and increased mitotic figures.The MVD value of colorectal tumors in AOM/DSS+EGCG group was higher than that in AOM/DSS mice colorectal tumors(P<0.05).The number of intertumoral macrophages in the AOM/DSS+EGCG group was also significantly higher than that in the AOM/DSS mice,and the difference was statistically significant(P<0.05).Conclusion:AOM/DSS is an effective method for short-term construction of a mouse colorectal adenoma model.Oral EGCG aggravates the formation of colorectal adenoma induced by AOM/DSS in mice.EGCG increased expression of CD31 and CD68 in colorectal tumor tissues of AOM/DSS model mice,which is likely to promote colitisrelated colorectal tumors by promoting angiogenesis... |
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