Baggetto L G
IBCP, UPR 412 CNRS, Lyon, France.
J Bioenerg Biomembr. 1997 Aug;29(4):401-13. doi: 10.1023/a:1022459100409.
Among the genetic and metabolic alterations that cancer cells undergo, several allow their survival under extreme environmental conditions. The resulting aberrant metabolism is compatible with tumor progression at the expenses of high energy needs, especially for maintaining high division rate. When treated with chemotherapeutic drugs many cancer cells take advantage of their ability to develop a resistance phenotype, as part of an adaptative mechanism. Two main actors of this multidrug phenotype (MDR) are represented by the P-glycoprotein and by the more recently discovered multidrug-resistance associated protein (MRP), two membrane proteins of the ABC superfamily of transporters that can extrude chemotherapeutic drugs under an ATP-dependent mechanism. We will briefly review the major metabolic aberrations that several cancers develop, followed by the molecular, genetic, structural, and functional aspects related mainly to P-glycoprotein, with a concern for the regulation of mdr gene expression. We will point out the role that membrane cholesterol may play in the MDR phenotype, relate this phenotype to bioenergetic considerations, and review the ways of modulating it by the use of new therapeutic approaches.
在癌细胞经历的基因和代谢改变中，有几种改变使它们能够在极端环境条件下存活。由此产生的异常代谢与肿瘤进展相适应，但以高能量需求为代价，尤其是为了维持高分裂率。当用化疗药物治疗时，许多癌细胞利用其产生耐药表型的能力，作为一种适应性机制的一部分。这种多药耐药表型（MDR）的两个主要作用因子是P-糖蛋白和最近发现的多药耐药相关蛋白（MRP），它们是ABC转运蛋白超家族的两种膜蛋白，能够通过ATP依赖机制排出化疗药物。我们将简要回顾几种癌症所发生的主要代谢异常，随后主要介绍与P-糖蛋白相关的分子、遗传、结构和功能方面，同时关注mdr基因表达的调控。我们将指出膜胆固醇在MDR表型中可能发挥的作用，将这种表型与生物能量学因素联系起来，并回顾使用新治疗方法对其进行调节的方式。
