Lavie Y, Liscovitch M
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Glycoconj J. 2000 Mar-Apr;17(3 -4):253-9. doi: 10.1023/a:1026553626537.
The carcinogenic process involves a complex series of genetic and biochemical changes that enables transformed cells to proliferate, migrate to secondary sites and, in some cases, acquire mechanisms that make cancer cells resistant to chemotherapy. This phenomenon in its most common form is known as multidrug resistance (MDR). It is usually mediated by overexpression of P-glycoprotein (P-gp) or other plasma membrane ATPases that export cytotoxic drugs used in chemotherapy, thereby reducing their efficacy. However, additional adaptive changes are likely to be required in order to confer a full MDR phenotype. Recent studies have shown that acquisition of MDR is accompanied by upregulation of lipids and proteins that constitute lipid rafts and caveolar membranes, notably glucosylceramide and caveolin. These changes may be related to the fact that in MDR cells a significant fraction of cellular P-gp is associated with caveolin-rich membrane domains, they may be involved in drug transport and they could have an impact on drug-induced apoptosis and on the phenotypic transformation of MDR cancer cells.
致癌过程涉及一系列复杂的基因和生化变化，这些变化使转化细胞能够增殖、迁移至继发部位，并且在某些情况下获得使癌细胞对化疗产生抗性的机制。这种现象最常见的形式被称为多药耐药性（MDR）。它通常由P-糖蛋白（P-gp）或其他质膜ATP酶的过表达介导，这些酶会输出化疗中使用的细胞毒性药物，从而降低其疗效。然而，可能还需要其他适应性变化才能赋予完整的MDR表型。最近的研究表明，获得MDR伴随着构成脂筏和小窝膜的脂质和蛋白质的上调，特别是葡萄糖神经酰胺和小窝蛋白。这些变化可能与以下事实有关：在MDR细胞中，相当一部分细胞P-gp与富含小窝蛋白的膜结构域相关联，它们可能参与药物转运，并且可能对药物诱导的细胞凋亡以及MDR癌细胞的表型转化产生影响。
