title: Adiponectin deficiency: role in chronic inflammation induced colon cancer.
abstract: Adiponectin (APN), an adipokine, exerts an anti-inflammatory and anti-cancerous activity with its role in glucose and lipid metabolism and its absence related to several obesity related malignancies including colorectal cancer. The aim of this study is to determine the effect of APN deficiency on the chronic inflammation-induced colon cancer. This was achieved by inducing inflammation and colon cancer in both APN knockout (KO) and C57B1/6 wild type (WT) mice. They were divided into four treatment groups (n=6): 1) control (no treatment); 2) treatment with three cycles of dextran sodium sulfate (DSS); 3) weekly doses of 1,2-dimethylhydrazine (DMH) (20mg/kg of mouse body weight) for twelve weeks; 4) a single dose of DMH followed by 3 cycles of DSS (DMH+DSS). Mice were observed for diarrhea, stool hemoccult, and weight loss and were sacrificed on day 153. Tumor area and number were counted. Colonic tissues were collected for Western blot and immunohistochemistry analyses. APNKO mice were more protected than WT mice from DSS induced colitis during first DSS cycle, but lost this protection during the second and the third DSS cycles. APNKO mice had significantly severe symptoms and showed greater number and larger area of tumors with higher immune cell infiltration and inflammation than WT mice. This result was further confirmed by proteomic study including pSTAT3, pAMPK and Cox-2 by western blot and Immunohistochemistry. Conclusively, APN deficiency contributes to inflammation-induced colon cancer. Hence, APN may play an important role in colorectal cancer prevention by modulating genes involved in chronic inflammation and tumorigenesis.
authors.affiliation: Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, 921 Assembly Street, Room 402, USA.
authors.forename: Arpit
authors.initials: A
authors.lastname: Saxena
authors.forename: Alexander
authors.initials: A
authors.lastname: Chumanevich
authors.forename: Emma
authors.initials: E
authors.lastname: Fletcher
authors.forename: Bianca
authors.initials: B
authors.lastname: Larsen
authors.forename: Kirby
authors.initials: K
authors.lastname: Lattwein
authors.forename: Kamaljeet
authors.initials: K
authors.lastname: Kaur
authors.forename: Raja
authors.initials: R
authors.lastname: Fayad
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics*; D000818:Animals; D002908:Chronic Disease; D003110:Colonic Neoplasms / Q000209:etiology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D052242:Adiponectin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D051546:Cyclooxygenase 2; D000263:Adenylate Kinase