Reversal of multidrug resistance mediated by P-Glycoprotein / 中国临床药理学与治疗学

ABSTRACT

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.