Diabetes promotes DMH-induced colorectal cancer by increasing the activity of glycolytic enzymes in rats

• Published in: PloS one Vol. 9; no. 10; p. e110455
• Main Authors: Jia, Yanglei, Xu, Gang, Zhou, Wenjing, Wang, Zhenzheng, Meng, Linlin, Zhou, Songnan, Xu, Xia, Yuan, Huiqing, Tian, Keli
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.10.2014; Public Library of Science (PLoS)
• Subjects: Aberrant Crypt Foci - pathology; Animal models; Animal tissues; Animals; Biochemistry; Bioengineering; Cancer; Carcinogenesis; Carcinogens; Cell cycle; Cell growth; Colon; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - etiology; Colorectal Neoplasms - pathology; Crypts; Dehydrogenases; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - complications; Enzymes; Glucose metabolism; Glycolysis; Health risks; Hexokinase - metabolism; Histological Techniques; Hydrazines - toxicity; Hyperglycemia; Incidence; Insulin resistance; Kinases; Laboratory animals; Male; Medical research; Medicine; Medicine and Health Sciences; Metabolism; Molecular biology; Phosphorylation; Proliferating Cell Nuclear Antigen - metabolism; Protein Serine-Threonine Kinases - metabolism; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Pyruvate Kinase - metabolism; Rats; Rats, Sprague-Dawley; Rodents; Sulfhydryl Compounds - toxicity; Tumors; Beijing China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0110455

The objective of the present study was to investigate the association between diabetes mellitus and colorectal carcinogenesis as well as the possible mechanism involved in this interaction. Diabetes rat models were induced with a low dose of STZ followed by a low dose of DMH to induce colorectal cancer. The formation of ACF in the colon and the incidence, number and size of tumors were measured. The activity of glycolytic enzymes in colonic tissues was also measured. The results demonstrated that both the total number of ACF and the number of foci that contain a different number of crypts were increased in diabetic rats. At the end of the experimental treatment, the incidence, number and size of tumors were also increased in diabetic rats. Overall, these data indicated that diabetes increased the risk of colorectal cancer. The activity of HK and PK in colonic tissues was increased in diabetic rats, whereas the activity of PDH was decreased. In addition, the activities of these enzymes in intratumor were higher than that of in peritumor. These data indicated that the high rate of glycolysis may play a role in colorectal carcinogenesis in diabetic rats.