Objective: To confirm that the severity of inflammation can promote the colitis-associated colorectal cancer(CAC) and explore the function of STAT3 signal pathway in CAC.
Methods: Mutagenic agent azoxymethane(AOM) and pro-inflammatory agent dextran sodium sulfate salt (DSS) were used to develop a mouse model of CAC. By changing the concentration of DSS (0, 1% and 2% respectively), the mouse model with different extent of severity of inflammation was developed and the risk of carcinogenesis among these groups was compared. The expression of STAT3 signal pathway was detected by immunohistochemistry staining.
Results: In the evaluation of inflammatory severity, disease activity index, histopathological inflammation scores and the expression of pro-inflammation chemokines such as TNF-α, IL-6 and IL-12 in the higher inflammatory response group were higher than that in the lower inflammatory response group. The incidence of colorectal tumor was 100%(12/12) in the higher inflammatory response group and the incidence of colorectal tumor was 58.3%(7/12) in the lower inflammatory response group, and the difference between these two group was statistically significant (P<0.05). The multiplicity(number of tumors/colon) was 12.5±0.5 in the higher inflammatory response group and the multiplicity was 6.6±1.0 in the lower inflammatory response group, and the difference between these two groups was statistically significant (P<0.001). The tumor load(sum of tumor diameters per mouse) in the higher inflammatory response group was 44.2±2.4 mm and that in the lower inflammatory response group was only 18.7±2.7 mm, and the difference between these two groups was statistically significant (P<0.0001). Moreover, the expression of p-STAT3 (Tyr705) was higher in colitis tissue of the higher inflammatory response group than that of the lower inflammatory response group.
Conclusions: Inflammation can promote the colitis-associated CAC. And the activation of STAT3 signal pathway may promote the development of CAC.