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首页> 外文期刊>Biochemical Pharmacology >Hypoxia increases tumor cell sensitivity to glycolytic inhibitors: a strategy for solid tumor therapy (Model C).
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Hypoxia increases tumor cell sensitivity to glycolytic inhibitors: a strategy for solid tumor therapy (Model C).

机译：缺氧增加了肿瘤细胞对糖酵解抑制剂的敏感性：一种用于实体瘤治疗的策略（模型C）。

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Previously, we reported that two distinct in vitro tumor cell models of hypoxia (Models A and B) are hypersensitive to glycolytic inhibitors such as 2-deoxy-D-glucose (2-DG) and oxamate [Liu et al., Biochemistry 2001;40:5542-7]. Model A consists of osteosarcoma cells (143B) treated with agents that interfere with mitochondrial oxidative phosphorylation (OxPhos), and Model B represents rho(0) cells, a variant derived from 143B cells, which, due to their deficiency in mitochondrial DNA, cannot perform OxPhos. Extending these studies, we report here on Model C, which is composed of 143B cells grown under various levels of external O(2) (0, 0.1, 0.5, 1, 5, 10, and 21%). At the lower levels of O(2) that we tested, 143B cells were hypersensitive to 2-DG and oxamate when compared with cells grown at a normal level of O(2). In contrast, 143B cells under hypoxic or aerobic conditions showed equal sensitivity to a standard chemotherapeutic agent, vinblastine. Furthermore, when treated under reduced O(2) amounts, rho(0) cells displayed no hypersensitivity to 2-DG and, in fact, were slightly more resistant than under aerobic conditions. At 0-5% O(2) levels, untreated 143B cells displayed reduced growth and elevated lactic acid levels, while rho(0) cell growth remained unaffected except at 0% O(2) where growth was inhibited by 19%. The results with Model C are in agreement with our previous data using Models A and B, and extend these studies by illustrating that within a wide range of hypoxia the growth of tumor cells is retarded and that these slow-growing cells become hypersensitized to glycolytic inhibitors. Taken together with Models A and B, the data with Model C support our hypothesis that the hypoxic environment of slow-growing cells found in the inner core of solid tumors renders them amenable to selective targeting with glycolytic inhibitors.
机译：以前，我们报道了两个不同的体外缺氧肿瘤细胞模型（模型A和B）对糖酵解抑制剂（例如2-脱氧-D-葡萄糖（2-DG）和草酸盐）高度敏感[Liu等人，Biochemistry 2001; 2001年。 40：5542-7]。模型A由用干扰线粒体氧化磷酸化（OxPhos）的试剂处理的骨肉瘤细胞（143B）组成，模型B代表rho（0）细胞，它是衍生自143B细胞的一种变体，由于其线粒体DNA缺乏，因此不能执行OxPhos。扩展这些研究，我们在这里报告模型C，该模型由在各种水平的外部O（2）（0、0.1、0.5、1、5、10和21％）下生长的143B细胞组成。在我们测试的O（2）较低的水平下，与在正常水平的O（2）下生长的细胞相比，143B细胞对2-DG和草酸酯高度敏感。相反，在缺氧或有氧条件下的143B细胞对标准化学治疗剂长春碱具有相同的敏感性。此外，当在减少的O（2）量下处理时，rho（0）细胞没有显示出对2-DG的超敏性，并且实际上比有氧条件下的抵抗力略强。在0-5％的O（2）水平下，未经处理的143B细胞显示出减少的生长和升高的乳酸水平，而rho（0）细胞的生长保持不受影响，除了在0％的O（2）处生长受到19％抑制。模型C的结果与我们先前使用模型A和B的数据相符，并且通过说明在广泛的缺氧范围内肿瘤细胞的生长受到阻滞并且这些缓慢生长的细胞对糖酵解抑制剂过敏而扩展了这些研究。 。与模型A和模型B一起使用，模型C的数据支持了我们的假设，即在实体瘤的内部核心中发现的缓慢生长的细胞的低氧环境使其适合糖酵解抑制剂的选择性靶向。

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