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

Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase
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DOI:
10.1016/s0304-3835(01)00667-x
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发表时间:
2001-11-08
期刊:
影响因子:
9.7
通讯作者:
Geschwind, JF
Geschwind, JF
中科院分区:
医学1区
文献类型:
--
作者:
Ko, YH;Pedersen, PL;Geschwind, JF

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兔VX2肿瘤植入肝脏后,已被证明是研究肝细胞癌的方便模型。然而,其代谢特性尚未得到很好的研究。值得注意的是,本文所描述的研究表明,VX2肿瘤在兔肝脏植入和生长后表现出高糖酵解/高己糖激酶表型。此外,有限筛选结果显示,2-脱氧葡萄糖(2DOG)和3-溴丙酮酸(3BrPA)对糖酵解速率的抑制效果最好,前者被己糖激酶磷酸化而不进一步代谢,后者直接抑制己糖激酶。最后,当对培养的肝癌细胞进行测试时,两种抑制剂都促进了细胞死亡。这些研究强调了VX2肿瘤模型在晚期肝癌研究和选择抗肝癌药物方面的有用性。(C) 2001爱思唯尔科学爱尔兰有限公司版权所有。
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.