Analysis of metabonomic profiling alterations in a mouse model of colitis-associated cancer and 2-deoxy-d-glucose treatment

Abstract

Inflammation is well recognized to be associated with tumorigenesis, cancer progression and tumor metabolism of colorectal cancer (CRC). 2-Deoxy-D-glucose (2-DG), a glycolytic inhibitor, has been reported to possess anticancer properties and is considered to be a promising treatment for tumors. However, the metabolic alteration in tumorigenesis caused by inflammation and 2-DG prevention remains elusive. In this study, a gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) analysis was applied to investigate the anticancer activity of 2-DG on the alteration of metabolites in a colitis-associated cancer model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). The data showed that 2-DG obviously decreased the incidence of tumor formation induced by AOM and DSS. 14 metabolites were significantly decreased in the AOM/DSS group, while all these metabolites were reversed by 2-DG treatment. Furthermore, metabolic pathway analysis (MetPA) was introduced to reveal the involvement of four metabolic networks including linoleic acid metabolism, pentose phosphate pathway, nicotinate and nicotinamide metabolism and inositol phosphate metabolism. The significantly altered metabolites of linoleic acid, nicotinamide, ribose-5-phosphate and myo-inositol were involved in these four pathways. Moreover, the expression of PKM2, which was induced by AOM and DSS, was attenuated by 2-DG treatment. Together, this study provides an insight into how 2-DG shows anticancer effects and may serve as a therapeutic agent for colitis-associated cancer.