Characterization of a novel metabolic strategy used by drug-resistant tumor cells
Characterization of a novel metabolic strategy used by drug-resistant tumor cells
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DOI：
10.1096/fj.02-0541com
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发表时间：
2002-10-01
期刊：
影响因子：
4.8
通讯作者：
Newell, MK
中科院分区：
文献类型：
--
作者：
Harper, ME;Antoniou, A;Newell, MK
获得性或固有的耐药性是实现成功癌症治疗的主要问题。然而，多效性耐药的机制仍然不清楚。我们已经确定并表征了一种区分耐药细胞和药物敏感细胞的细胞代谢策略。这种策略可能有助于保护耐药细胞免受化疗药物和辐射造成的损害。我们发现，耐药细胞的线粒体膜电位较低，当葡萄糖有限时，它们会使用非葡萄糖碳源（脂肪酸）来消耗线粒体氧，并且可以免受辐射等外源应激的影响。此外，耐药细胞表达高水平的线粒体解偶联蛋白2 (UCP2)。这种代谢策略的发现可能有助于设计新的耐药治疗方法。
Acquired or inherent drug resistance is the major problem in achieving successful cancer treatment. However, the mechanism(s) of pleiotropic drug resistance remains obscure. We have identified and characterized a cellular metabolic strategy that differentiates drug-resistant cells from drug-sensitive cells. This strategy may serve to protect drug-resistant cells from damage caused by chemotherapeutic agents and radiation. We show that drug-resistant cells have low mitochondrial membrane potential, use nonglucose carbon sources (fatty acids) for mitochondrial oxygen consumption when glucose becomes limited, and are protected from exogenous stress such as radiation. In addition, drug-resistant cells express high levels of mitochondrial uncoupling protein 2 (UCP2). The discovery of this metabolic strategy potentially facilitates the design of novel therapeutic approaches to drug resistance.