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

被引:297
作者
Ko, YH
Pedersen, PL
Geschwind, JF
机构
[1] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Div Cardiovasc & Intervent Radiol, Baltimore, MD 21205 USA
关键词
liver cancer; tumor metabolism; hexokinase; drug targeting; 2-deoxy glucose; 3-bromo pyruvate;
D O I
10.1016/S0304-3835(01)00667-X
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:83 / 91
页数:9
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