Oudard S, Miccoli L, Dutrillaux B, Poupon M F
Unité mixte de recherche 147 CNRS, Paris.
Bull Cancer. 1998 Jul;85(7):622-6.
Loss of chromosomes is a recurrent event in cancer. Chromosome-10 losses occur with tumor progression and characterize advanced gliomas. This chromosome carries many genes involved in glucose metabolism. Hexokinase (HK) gene is located on chromosome-10. Hexokinase enzymatic activity is decreased in glioblastomas. Hexokinase enables glucose entry into glycolysis and is critical for these highly glycolytic tumors. These enzyme is either free in the cytosol or bound to the mitochondrial outer membrane. Disturbance of HK binding to mitochondria by lonidamine led to inhibition of cells and xenografted-glioma growth. Hexokinase bind to a mitochondrial porin which involved peripheral benzodiazepine receptors. Inhibition of HK and peripheral benzodiazepine receptors by lonidamine and diazepam led to synergistic antitumoral activity in xenografted gliomas. Co-inhibition of these two receptors will lead to a decrease in glycolysis, often elevated in these tumors, without modifying energetic metabolism of normal cells.
染色体缺失是癌症中反复出现的事件。随着肿瘤进展会出现10号染色体缺失，这是高级别胶质瘤的特征。这条染色体携带许多参与葡萄糖代谢的基因。己糖激酶（HK）基因位于10号染色体上。胶质母细胞瘤中己糖激酶的酶活性降低。己糖激酶使葡萄糖进入糖酵解过程，对这些高度糖酵解的肿瘤至关重要。这种酶要么游离于细胞质中，要么与线粒体外膜结合。洛尼达明干扰己糖激酶与线粒体的结合会导致细胞和异种移植胶质瘤生长受到抑制。己糖激酶与一种涉及外周苯二氮䓬受体的线粒体孔蛋白结合。洛尼达明和地西泮对己糖激酶和外周苯二氮䓬受体的抑制导致异种移植胶质瘤产生协同抗肿瘤活性。共同抑制这两种受体会导致糖酵解减少，而糖酵解在这些肿瘤中通常会升高，同时不会改变正常细胞的能量代谢。
