Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice

Abstract

AIM:To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model, and to determine the contribution of adiponectin deficiency to colorectal cancer development and proliferation. METHODS: We examined the influence of adiponectin deficiency on colorectal carcinogenesis induced by the administration of azoxymethane (AOM) (7.5 mg/kg, intraperitoneal injection once a week for 8 wk), by using adiponectin-knockout (KO) mice. RESULTS: At 53 wk after the first AOM treatment, KO mice developed larger and histologically more progressive colorectal tumors with greater frequency compared with wild-type (WT) mice, although the tumor incidence was not different between WT and KO mice. KO mice showed increased cell proliferation of colorectal tumor cells, which correlated with the expression levels of cyclooxygenase-2 (COX-2) in the colorectal tumors. In addition, KO mice showed higher incidence and frequency of liver tumors after AOM treatment. Thirteen percent of WT mice developed liver tumors, and these WT mice had only a single tumor. In contrast, 50% of KO mice developed liver tumors, and 58% of these KO mice had multiple tumors. CONCLUSION: Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice. This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.

The Role of Adipocytokines in Colon Cancer and Adenomas / Uloga Adipocitokina U Kanceru I Adenomima Debelog Creva

“…Furthermore, colon adenoma formation is promoted by the deficiency of adiponectin and colonic epithelial cell pro-J Med Biochem 2014; 33 (2) 139 liferation is increased in animals fed a high-fat diet (13). In addition to these results, a significant decrease was observed in AMPK phosphorylation in intestinal epithelial cells of adiponectin-knockout mice compared with the control group (19).…”

Adiponectin action from head to toe

“…Finally, the induction of colorectal cancer in wild-type and adiponectin knockout mice resulted in an increase in the number, volume and aggressiveness of, as well as in the occurrence of metastasis from, colorectal tumors in adiponectin knockout mice when compared to wild-type mice [267]. Moreover, COX-2 expression in the colorectal tumors of adiponectin-deficient mice was higher relative to wild-type mice.…”

“…Moreover, COX-2 expression in the colorectal tumors of adiponectin-deficient mice was higher relative to wild-type mice. Given that COX-2 is a well-established pathogenic factor in colorectal carcinogenesis, those findings further suggest that adiponectin may play a protective role against colorectal cancer development [267]. Working on two independent case-control studies, Kaklamani et al [268] recently reported that individuals with the adiponectin rs266729 (-11365 C ?…”

Adiponectin and the cardiometabolic syndrome: An epidemiological perspective

“…Experimentally, colorectal tumours induced by azoxymethane were histologically more progressive with greater frequency in adiponectin-knockout mice 71 . At present, however, little is known about the molecular mechanism of enhanced tumour formation and growth in adiponectin deficiency and further studies are needed.…”