Experimental Study Of Colitis-associated Colorectal Cancer Tongxieyaofang Regulation TGF-?/SMAD4 Signaling Pathway Intervention

?Objective?Colon cancer,as a common malignant tumor in China,has an increasing trend in recent years,and patients with inflammatory bowel disease have a high probability of progressing into malignant colon cancer.In the process of preventing inflammation from further developing into cancer,traditional Chinese medicine has a good preventive effect,but in the process of “inflammatory-cancer” transformation,involving multiple signaling pathways,the relevant mechanism for intervention of Chinese medicine is not clear..Through the establishment of relevant disease models and detection of major related cytokines,the mechanism of Chinese medicine intervention in colitis-related colon cancer was discussed.?Methods?The animal model of colitis-associated colon cancer was successfully replicated by AOM combined with DSS.The high,medium and low doses of Tongxie Yaofang were used for intragastric administration and compared with positive drugs.During the experiment,we used the mouse disease activity index and regular weighing to judge the general situation.We randomly selected the mice at a certain time point to take the samples,measured the length of the colon,and observed the infiltration of inflammatory cells and intestinal tract under HE staining.The expression of TGF-?1 and SMAD4 in mouse colon was observed by immunohistochemistry.The contents of TNF-? and CCL20 in serum were detected by ELISA.The TNF-? mRNA in mouse colon was detected by RT-PCR.,CCL20 mRNA expression.?Results?1.Modeling time lasted for 7 weeks for a total of 49 days.At the 4th week and the 5th peripheral high inflammation period,the mice showed weight loss,hair loss,loose stools and blood in the stool during the experimental period.After the material was taken,the intestinal tissues were observed.Inflammatory cells invade and become cancerous.2.Compared with the blank group,the disease activity index,body weight change and colon length of the model group(P<0.01)were significantly different.Compared with the model group,the positive group,the high-dose group of Tongxie Yaofang,and the diarrhea The main dose group,the low-dose group of Tongxie Yaofang,the disease activity index(P<0.05),the difference was significant;the high-dose group of Tongxie Yaofang,the middle dose group of Tongxie Yaoji,and the low-dose group of Tongxie Yaofang In contrast,the effect of the middle dose group of Tongxie Yaofang was the closest to the positive group;after drug intervention,the expression of SMAD4 in the colon tissue of the blank group was higher than that of the other groups(P<0.01).Compared with the model group,the expression of SMAD4 in the positive group was higher.High(P<0.05),the expression of SMAD4 in the middle dose group of Tongxie Yaofang(P<0.05).Pain and diarrhea can increase the expression of SMAD4 in the colon.Compared with the blank group,the expression of TGF-?1 in the model group was significantly different(P<0.01).Compared with the model group,the expression of TGF-?1 in the positive group(P<0.05)and the expression of TGF-?14 in the middle dose group of Tongxie Yaofang.(P<0.05);Compared with the blank group,the serum levels of TNF-? and CCL20 in the model group were significantly different(P<0.01).Compared with the model group,the serum levels of TNF-? and CCL20 in the positive group(P< 0.05),serum TNF-?,CCL20 content in the middle dose group of Tongxie Yaofang(P<0.05);compared with the blank group,the expression of TNF-? mRNA and CCL20 mRNA in the model group was very different(P<0.01).Significantly;compared with the model group,the expression of TNF-? mRNA and CCL20 mRNA in the positive group(P<0.05),and the expression of TNF-? mRNA and CCL20 mRNA in the middle dose group of Tongxie Yaofang(P<0.05).Tongxie Yaofang can reduce the expression of TNF-? and CCL20 in serum and tissues of the colon,and has a certain intervention effect on inhibiting the progression of colitis to colon cancer.?Conclusions?1.Tongxie Yaofang has a benign intervention effect on the evolution of colitis-related colon cancer 2.Tongxie Yaofang can increase the content of TGF-?1 and SMAD4 in colonic mucosa and play a role in inhibiting the development of inflammation.3.The mechanism of diarrhea and diarrhea intervention in colitis-related colorectal cancer may be related to up-regulation of TGF-?1 and SMAD4 inhibition of TNF-? and CCL20 expression.