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Based On EMT To Explore The Preventive Effect Of Wumeiwan On Colitis-associated Colorectal Cancer

Posted on:2019-04-25Degree:MasterType:Thesis
Country:ChinaCandidate:M H LiuFull Text:PDF
GTID:2404330545462344Subject:Traditional surgery
Abstract/Summary:PDF Full Text Request
Background and purpose:Colitis-related colorectal cancer,a serious threat to human life and health.Wumeiwan is a classic name from the "Treatise on Febrile Diseases" and has a definite curative effect on inflammatory bowel disease.Based on this,this experiment aims to investigate the preventive effect of Wumeiwan decoction on colitis-related colorectal cancer and its possible Potential mechanism.Methods:Eighty C57 male mice were randomly divided into blank group(10 rats),model group(20 rats),aspirin positive control group(20 rats),Wumeiwan equivalent dose group(15 rats),and Wumeiwan Dose group(15).The blank group was fed normally and the other groups replicated AOM/DSS-induced colitis-associated colorectal cancer models.At the beginning of the 5th week of the experiment,the drug intervention was carried out until the end of the 15th weekend.The model group was intragastrically administrated with the same volume of normal saline and aspirin positive control group by intragastric administration with aspirin solution and the equivalent dose of Wumeiwan was intragastrically administered at the equivalent dose.Wumeiwan decoction and Wumeiwan high-dose group were given 1.5 times the clinical equivalent dose of Wumeiwan decoction.The general condition of mice,body weight changes,disease activity index,number of colon tumors,colorectal length,colorectal mass/length were recorded;serum IL-6 levels were detected by ELISA;EMT-related protein expression was detected by Western Blot..result:1.Wumeiwan decoction can improve the general condition of model mice and increase the survival rate of mice.The mice in the model group exhibited significant mental fatigue,dietary loss,loose hair,etc.,and weight loss was significantly reduced.After intervention of Wumeiwan,the above symptoms of the mice were significantly improved,but the weight was increased,but there was no statistical difference;model group mice The survival rate was only 35%(7/20),the survival rate of the Wumeiwan equivalent dose group was 80%(12/15),and the survival rate of the high-dose Wumeiwan group was 66.7%(10/15).Therefore,it can be seen that Wumeiwan It can significantly improve the survival rate of mice,in which the equivalent dose of Wumeiwan decoction to improve the survival rate of mice better,there is a statistical difference(P<0.01).2.Wumeiwan decoction can reduce the index of disease activity in the late mouse modelling periodAfter the second DSS was used for personal use,the DAI of the model group was 0.78±0.983,the equivalent dose of Wumeiwan was 0.619±0.853,and the high dose of Wumeiwan was 0.641±0.756.Although the Wumeiwan group was better than the model group,there was no statistics.Significance:After the third DSS drinking,the model group's DAI was 3.43±0.38,the Wumeiwan equivalent dose group was 1.95±0.75,and the Wumeiwan high dose group was 2.15±1.08.Wumeiwans can significantly reduce the mouse model.DAI index(P<0.01)3.Wumeiwan can reduce the number and volume of tumors in CAC miceThe mice in the blank group had no tumors in the intestine.Compared with the blank group,the number of tumors in the model group was higher(P<0.01),and the number of tumors greater than or equal to 3 mm was more(P<0.01);In comparison,the number of intestinal tumors and the number of tumors with a diameter greater than or equal to 3 mm were reduced in the Wumeiwan treatment group,in which the equivalent dose group was significantly reduced(P<0.01),and the total number of high-dose tumors was reduced(P<0.05).However,there was no statistical difference in the number of tumors with a diameter greater than or equal to 3 mm.There was no statistical difference between the treatment groups.4.Wumeiwan can increase the length of colorectal cancer in CAC mice and reduce the color and length of the colorectum.Compared with the blank group,the colorectal length of the mice in the model group was significantly shortened and the colon mass/length was significantly increased,both of which had statistically significant differences(P<0.01).Compared with the mice in the model group,the length of the colorectum and the mass/length of the colon were decreased in the Wumeiwan treatment group.The colorectal lengths of the mice in the equivalent and high dose groups were significantly increased(P<0.01).The mass/length of the colon was significantly reduced(P<0.01),and the mass/length of the high-dose group was also decreased(P<0.05);the number of tumors in the intestine and the number of tumors with a diameter of 3 mm or more were all reduced,and the equivalent dose group was two.All significantly decreased(P<0.01).5.Wumeiwan can reduce IL-6 concentration in mouse serumCompared with the blank group,the serum IL-6 concentration in the model group was significantly higher(P<0.01);after intervention of the Wumeiwan,compared with the model group mice,the serum IL-6 level of he Wumeiwan mouse The concentration was significantly decreased and there was a statistical difference(P<0.01)6.Wumeiwan can reverse the expression of colorectal EMT-related proteins in CAC miceCompared with the blank group,the expression of E-cad in the colon tumor tissue of the mice in the model group was significantly lower(P<0.01);compared with the model group,the Wumeiwan equivalent dose group and the Wumeiwan high dose group mice colon The expression of E-cad in tumor tissues was significantly increased and the difference was statistically significant(P<0.01).Compared with the blank group,the expression of N-cad in the colon tumor tissue of mice in the model group was significantly higher(P<0.01);compared with the model group,the Wumeiwan equivalent dose group and the Wumeiwan high dose group mice The expression of N-cad in colon cancer tissue decreased,and the difference was statistically significant(P<0.05).Compared with the blank group,the expression of Vimentin in the colon tumor tissues of the mice in the model group was significantly higher(P<0.01);compared with the model group,the mice in the equivalent dose group of Wumeiwan had colon tumors.The expression of Vimentin in the tissues decreased,and the difference was statistically significant(P<0.05),but there was no statistical difference in the high-dose group.Compared with the blank group,Snail expression in the colon tumor tissues of the mice in the model group was significantly higher(P<0.01).Compared with the model group,the Snail expression in the colon tumor tissues of the Wumeiwan equivalent dose group was decreased.The difference was statistically significant(P<0.05),but there was no statistical difference in the high-dose group.Conclusion:1.Wumeiwan Decoction has a good preventive effect on AOM/DSS-induced colitis-associated colorectal cancer;2The mechanism of action of Wumeiwan decoction in preventing colitis-associated colorectal cancer may be related to the decrease of IL-6 concentration in serum and EMT of colorectal tissue.
Keywords/Search Tags:Wumeiwan, colorectal cancer, interleukin 6, epithelial-mesenchymal transition, E-cadherin
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