Biochemical, Genetic, and Metabolic Adaptations of Tumor Cells That Express the Typical Multidrug-Resistance Phenotype. Reversion by New Therapies：（生化、遗传和代谢适应表达典型的多药耐药性的肿瘤细胞表型。）.pdfVIP

Journal of Bioenergetics and Biomembranes, Vol. 29, No. 4, 1997 Biochemical, Genetic, and Metabolic Adaptations of Tumor Cells That Express the typical Multidrug-Resistance Phenotype. Reversion by New Therapies Loris G. Baggetto1 Received April 25, 1997; accepted My 15, 1997 Among the genetic and metabolic alterations that cancer cells undergo, several allow their survival under extreme environmental conditions. The resulting aberrant metabolism is compati- ble with tumor progression at the expenses of high energy needs, especially for maintaining high division rates. 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