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

Yanglei Jia,Keli Tian,Huiqing Yuan,Xia Xu,Linlin Meng,Gang Xu,Songnan Zhou,Wenjing Zhou,Zhenzheng Wang,Daotai Nie

doi:10.1371/journal.pone.0110455

Yanglei Jia, Keli Tian + Show 8 more

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https://doi.org/10.1371/journal.pone.0110455

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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.

Highlights

Colorectal cancer is a common gastrointestinal malignant tumors
Some results are inconsistent with this association because diabetes mellitus is a group of complex metabolic disorders characterized by hyperglycemia
One of the main objectives of the present work was to determine whether type 2 diabetes mellitus could increase the risk of colorectal cancer in an animal model

Summary

Introduction

Colorectal cancer is a common gastrointestinal malignant tumors. Several similar risk factors have been found between diabetes mellitus and colorectal cancer. Those include a ‘‘Western Lifestyle’’, with diets low in fruits and vegetables or fiber and high in fat and cooked meat, as well as restricted physical activity [3,4]. Epidemiologic findings to date have shown that type 2 diabetes mellitus is closely related to the increased risk of colorectal cancer [3,4,5,6,7,8]. Different epidemic factors from different countries, ethnicities and regions may influence the association between diabetes and cancer [3,7,9]

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