The therapeutic potential and deleterious effect of glucocorticoids on AOM/DSS-induced colorectal cancer in mice

Abstract Background Glucocorticoids (GCs) are widely used in the treatment of various autoimmune and inflammatory diseases, including inflammatory bowel disease (IBD), but the effect of GCs on the development of colitis-associated colorectal cancer (CAC) is largely undefined. Methods We first established azoxymethane and dextran sulfate sodium (AOM/DSS)-induced colorectal cancer and DSS-induced colitis in mice. Dexamethasone (DEX) was then administered at different periods of time to determine its effect on tumorigenesis and tumor progression. Moreover, body weight, stool property and fecal blood of mice were recorded. At the end of the study, the number and load of tumors were evaluated, and the expression of proteins associated with cell proliferation were measured. To evaluate the inflammation in colon, we detected the level of pro-inflammatory cytokine TNFα, and mucosal infiltration of inflammatory cells. Meanwhile, we also assessed the activity of MAPK/JNK pathway. Results AOM injection followed by three cycles of drinking water containing 1.5% DSS successfully induced multiple tumor formation in mouse colon and rectum. Both early and late DEX intervention suppressed tumor growth in mouse colorectum and significantly downregulated the expression of PCNA and cyclin D1. Meanwhile, DEX treatment significantly inhibited the TNFα production, mucosal infiltration of inflammatory cells and the activity of JNK pathway, which was more prominent in mice with early DEX intervention. However, DEX treatment deteriorated the general state of mouse manifested by greater loss of body weight and rectal bleeding. Conclusions Our data conclude that both early and late DEX intervention significantly ameliorate colonic inflammation and inhibit the development of AOM/DSS-induced colorectal cancer, at least partly due to the inhibition of MAPK/JNK pathway. However, the deleterious effect on the general condition of mouse may limit the duration of GCs treatment.