NF-κB/IL-6Pathway In Relation To The Colitis Associated Colorectal Cancer Development

Background and ObjectivesColorectal cancer (CRC) is one of the most common human cancers and has ahigh mortality worldwide. It is well known that chronis inflammation as seen inulcerative colitis（UC）significantly increases the risk of CRC, The development ofcolitis associated colorectal cancer (CAC) is similar to the classic colorectaladenoma-carcinoma sequence in many aspects, for instance, both of them developfrom the preformed cancer precursor-dysplasia and through a long term progressionand finally to CRC. However, CAC develops in the background of long-term chronicinflammation, and inflammatory factor is a main driving force for CAC.Since the incidence of UC in china is remarkably increased recently, the study ofCAC pathogenesis becomes necessary and important. Current evidence stronglysuggests that NF-κB/IL-6pathway is a key player in linking chronic inflammation toCAC. However, the dynamic change of the NF-κB/IL-6pathway during theestablishment of CAC has not been characterized. In this study, we evaluated thetiming and magnitude of NF-KB/IL-6pathway in relation to the procession of CAC.Materials and MethodsWe have examined the dynamic of the NF-κB/IL-6pathway in relation to the procession of experimental CAC induced by the administration of1.2-dimethylhydrazine (DMH) plus dextran sulfate sodium (DSS) in ICR male mice.CAC and control mice were sacrificed at one of4time-points:14,16,18, and22weeks of age. We evaluated the timing and magnitude of NF-KB/IL-6in male miceby the IHC and WB. The tumor burden、inflammation degree and the densities ofIL-6and NF-κB positive cells by SPSS15.0.ResultIntestinal tissue was analyzed for tumor burden, inflammation degree andprotein level of IL-6and NF-κB. The results show that tumor burden in the bowelswas gradually increased over the observed time-points (form14to22weeks)(P <0.05). Inflammation degree followed a similar pattern. IL-6and NF-κB wereexpressed by both the transformed epithelial cells and stromal cells, the densities ofIL-6and NF-κB positive cells was increased starting at week14, with furtherincreases at16weeks and18weeks, and reached to the peak at22weeks. Westernblotting data confirmed increased expressions of IL-6and NF-κB proteins starting atweek14and persisting to22weeks.ConclusionThe timing and magnitude of NF-κB/IL-6pathway in relation to CACdevelopment was gradually increased and associated with the progression of CAC.