Interleukin-6 promotes tumor progression in colitis-associated colorectal cancer through HIF-1α regulation.

ABSTRACT

Interleukin-6 (IL-6) is a well-known etiological factor of colitis-associated colorectal cancer (CAC) and has a significant role in CAC progression. In addition, hypoxia-inducible factor 1α (HIF-1α) serves a primary role in the progression of CAC. However, the association between IL-6 and HIF-1α during the progression of CAC remains unclear. To investigate this association, the present study induced CAC in a mouse model using azoxymethane and dextran sulfate sodium. In addition, an anti-IL-6 receptor antibody was used to inhibit IL-6. In this model, anti-IL-6 receptor antibody treatment significantly inhibited the development of CAC and the expression of HIF-1α, in colorectal adenomas and adenocarcinomas. In patients with CAC, the HIF-1α gene was demonstrated to be overexpressed in tumor tissue compared with adjacent non-malignant tissue. Furthermore, HIF-1α mRNA expression was positively correlated with serum IL-6 concentration. The results of the present study suggest that IL-6 promotes CAC progression, in the early stage of the disease, through HIF-1α regulation.