Intestinal Epithelial Tumor Formation Improves Resistance To DSS-induced Intestinal Inflammation In Mice Model

Background Colorectal cancer(CRC)is one of the most globally prevalent malignancy.Theoretically,CRC is derived from three main pathway,including"Adenoma-carcinoma" sequence,serrated pathway and inflammatory pathway.Among them,inflammatory pathway is the main theoretical background of this study.Experimental and clinical evidence suggest that chronic inflammation leads to the occurrence of cancer.The process from chronic inflammation to dysplasia to cancer is called inflammatory-tumor transformation.Inflammatory cells and inflammatory cytokines are indispensable parts of inflammatory tumor transformation.Interleukin-6 is a pleiotropic cytokine secreted by a variety of cells.It broadly participates in transferring information,activating and modulating the immune cells,mediating the proliferation,differentiation and activation of T and B cells,activating inflammatory reaction.For years of research,great body of evidence suggested that,IL-6 is crucial in promoting proliferation of intestinal epithelial cells,improve its resistance to DSS-induced inflammation,while knockdown of IL-6 could reduce tumor formation.The aim of this research is to explore the transformation process of "colitis to colorectal cancer",study changes on tissue and molecular level,find out expression level of various inflammatory factors in the acute and repairing period of intestinal mucosal epithelial inflammatory microenvironment.And to explain why,from our aspect,carcinogenic factor helps to protect inflamed intestinal tissue and the affected individual in the "inflammatory-carcinoma" transformation,to explore concrete link between the specific inflammatory factor during colitis and intestinal epithelial cell protection.To ultimately provide scientific theoretical basis to find out the potential therapeutic target for promoting the repair of intestinal epithelial and inhibiting the transformation of colitis into colorectal cancer.Methods 1.We established DSS-induced colitis model and AOM+DSS-induced colitis-associated colorectal cancer model in C57BL6/J mice,assessed difference between two groups,from multi-aspect evidence collected from scores of Disease Severity Score and Murine Endoscopic Index of Colitis Severity,weight curve,survival curve,and verified at histochemical level.2.Induced colitis in ApcMin/+ gene background and wild-type mice with DSS,also assessed difference between two groups from multi-aspect mentioned above.3.Screened related dataset from public database of gene chip,to analyze the changing expression level of inflammatory cytokines in DSS-induced colitis,and performed internal validation at molecular level in collected tissue from above-mentioned mice model.4.Confirmed the specific inflammatory cytokine(interleukin-6),bred il6-knockout homozygote mice,and induced colitis in them and wild-type mice,also conducted assessment as previous.Results 1.AOM+DSS induced colitis-associated colorectal cancer model could effectively induce intestinal mucosal neoplasm in mice.2.Colitis in AOM+DSS induced colitis-associated colorectal cancer model was lesser compared with DSS-induced mice.3.ApcMin/+ mice had better prognosis than wild-type mice after challenged by DSS-induced colitis.4.IL-6 highly expressed in inflamed intestinal tissue of colitis.5.116-knockout mice was more sensitive to DSS-induced colitis than wild-type mice.Conclusion When affected by carcinogenic factors(such as AOM),or with a genetic background for the spontaneous formation of colorectal tumors,the formation of intestinal tumors can reduce the damage of DSS-induced colitis to intestinal mucosa and play a protective role for the individual;Il-6 was increased in the acute phase of the DSS-induced colitis mice model,and the absence of I1-6 in the intestinal mucosal epithelium aggravated the symptoms of colitis,shortened survival time.