P-糖蛋白介导多药耐药性的逆转

多药耐药（multidrug resistance,MDR)，即肿瘤细胞在接触一种抗肿瘤药物后产生了耐受其它多种结构全然不同，作用机理也大相径庭的抗肿瘤药物的抗药性。mdr-1基因及由该基因编码的P－糖蛋白（P-gp,P-Glycoprotein)是MDR产生的重要机制之一。P－gp为能量依赖性药物外排泵，其功能是使细胞内药物浓度降低，药物的作用减弱或丧失，细胞由此获耐药性。因此应用能抑制P－gp的药物是逆转MDR的一个重要手段。自1981年Tsuruo等报道钙通道阻滞剂维拉帕米能阻断P－gp功能逆转小鼠白血病细胞MDR以来，寻找和研究抑制P－gp的药物已成为抗肿瘤药物研究的热点之一。本就近几年报道的直接与P－gp相互作用而逆转MDR的逆转剂作简要介绍，并讨论逆转P－gp介导的MDR化合物的理化特性及逆转作用的影响因素等诸方面的问题。

Reversal of multidrug resistance mediated by P-Glycoprotein

Multidrug resistance (MDR) is the phenomenon observed in tumor cells that describes the simultaneous emergence of cellular resistance to the cytotoxic attack by structurally and mechanism unrelated chemotherapeutic drugs. The mdr 1 gene was sufficient to confer the MDR phenotype, including the expression of the P Glycoprotein (P Gp). P Gp appears to play an important role in tumor cells by acting as an energy dependent efflux pump to remove various drugs from the cell before they have a chance to exert their cytotoxic effects. It is generally accepted that reversal or inhibition of P Gp function in tumor cells is an important way for modulating MDR. It has been demonstrated in the laboratory that MDR mediated by the P Gp may be modulated by a wide variety of compounds. These compounds , which include verapamil and cyclosporin, generally have little or no effect by themselves on the tumor cells, but when used in conjunction with antineoplastic agents, they decrease, and in some instances eliminate, MDR. This paper will introduce some new reversal agents and discuss their physical and chemical characteration and others.