Gottesman M M, Pastan I, Ambudkar S V
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Curr Opin Genet Dev. 1996 Oct;6(5):610-7. doi: 10.1016/s0959-437x(96)80091-8.
Although the phenomenon of simultaneous resistance to multiple cytotoxic drugs (multidrug resistance) in cancer cells has been discussed for more than two decades, and the human and mouse genes encoding an energy-dependent transporter (the multidrug transporter or P-glycoprotein) responsible for multidrug resistance were cloned 10 years ago, there is still considerable controversy about the mechanism of action of this efflux pump and its true biological function. This review summarizes the current research on the mechanism of action of the multidrug transporter, including the hydrophobic cleaner and altered partitioning models, the possible function of P-glycoprotein as a chloride and/or ATP channel, the role of phosphorylation in its function and fact and speculation about its physiological role.
尽管癌细胞对多种细胞毒性药物同时产生耐药性（多药耐药）的现象已被讨论了二十多年，且编码负责多药耐药的能量依赖性转运蛋白（多药转运蛋白或P-糖蛋白）的人类和小鼠基因在10年前就已被克隆，但关于这种外排泵的作用机制及其真正的生物学功能仍存在相当大的争议。这篇综述总结了目前关于多药转运蛋白作用机制的研究，包括疏水清洁剂和改变分配模型、P-糖蛋白作为氯离子和/或ATP通道的可能功能、磷酸化在其功能中的作用以及关于其生理作用的事实与推测。
