The role of adiponectin in chronic inflammation‐induced colon cancer

BACKGROUND Patients with inflammatory bowel disease are at increased risk for developing colorectal cancer. In addition, obesity, an established risk factor for colorectal cancer, is characterized by the accumulation of excessive adipose tissue, which is the source of adipokines. Adiponectin (APN), an adipokine decreased in obesity, is reduced in colorectal cancer patients where signal transducers and activators of transcription (STAT)-3 is overexpressed. Also, it increases adenosine mono-phosphate kinase (AMPK) activation which suppresses cell growth by inhibiting mammalian target of rapamycin (mTOR). AMPK and APN inhibit the activity of cycloxygenase (COX)-2. PURPOSE To demonstrate the role of APN in the prevention of chronic inflammation-induced colon cancer (CICC). METHODS Inflammation and colon cancer were induced in both APN knock out (KO) and C57Bl/6 wild type (WT) mice by dextran sodium sulfate (DSS) and 1,2-Dimethylhydrazine (DMH) treatment respectively. Mice were observed for diarrhea, stool haemoccult, and weight loss. RESULTS APN KO mice were prone to develop CICC. APNKO mice treated with DSS+DMH showed greater number and larger area of tumors and downregulation of phosphorylated AMPK and overexpression of pSTAT3 and COX-2 as compared to the WT mice. CONCLUSION APN may play an important role in the prevention of colorectal cancer by modulating genes involved in CICC. NIH P20 RR-017698.