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

PLoS One. 2014 Oct 17;9(10):e110455. doi: 10.1371/journal.pone.0110455. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aberrant Crypt Foci / pathology*
  • Animals
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / pathology
  • Diabetes Mellitus, Experimental / chemically induced*
  • Diabetes Mellitus, Experimental / complications*
  • Hexokinase / metabolism
  • Histological Techniques
  • Hydrazines / toxicity
  • Male
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Pyruvate Kinase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sulfhydryl Compounds / toxicity

Substances

  • Hydrazines
  • N,N'-dimethyl-N,N'-bis(mercaptoacetyl)hydrazine
  • Proliferating Cell Nuclear Antigen
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Sulfhydryl Compounds
  • Hexokinase
  • Pyruvate Kinase
  • Protein Serine-Threonine Kinases

Grants and funding

This work was supported by The Natural Science Foundation of Shandong Province (2009ZRB01346). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.