Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase

The rabbit VX2 tumor when implanted in the liver has proven convenient as a model for studying hepatocellular carcinomas. However, its metabolic prope rties have not been well studied. Significantly, studies described here sho w that the VX2 tumor exhibits a high glycolytic/high hexokinase phenotype t hat is retained following implantation and growth in rabbit liver. In addit ion, results of a limited screen show that the glycolytic rate is inhibited best by 2-deoxyglucose (2DOG) and 3-bromopyruvate (3BrPA), the former comp ound of which is phosphorylated by hexokinase but not further metabolized, while the latter directly inhibits hexokinase. Finally, when tested on hepa toma cells in culture both inhibitors facilitated cell death. These studies underscore the usefulness of the VX2 tumor model for the study of advanced liver cancer and for selecting anti-hepatoma agents. (C) 2001 Elsevier Sci ence Ireland Ltd. All rights reserved.