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 properties have not been well studied. Significantly, studies described here show that the VX2 tumor exhibits a high glycolytic/high hexokinase phenotype that is retained following implantation and growth in rabbit liver. In addition, results of a limited screen show that the glycolytic rate is inhibited best by 2-deoxyglucose (2DOG) and 3-bromopyruvate (3BrPA), the former compound of which is phosphorylated by hexokinase but not further metabolized, while the latter directly inhibits hexokinase. Finally, when tested on hepatoma 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.
Ko
Y H
YH
Department of Biological Chemistry, Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
Pedersen
P L
PL
Geschwind
J F
JF
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006593:Hexokinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D019344:Lactic Acid / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011773:Pyruvates / Q000494:pharmacology*; D011817:Rabbits
D000963:Antimetabolites; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011773:Pyruvates; D019344:Lactic Acid; C017092:bromopyruvate; D003847:Deoxyglucose; D006593:Hexokinase; D005947:Glucose