Devine S E, Melera P W
Department of Biological Chemistry, University of Maryland School of Medicine, Baltimore 21201.
Cancer Chemother Pharmacol. 1994;33(6):465-71. doi: 10.1007/BF00686502.
Hamster cells grown in culture may, like human and mouse cells, develop multidrug resistance (MDR) when exposed to certain cytotoxic chemotherapeutic agents. Several phenotypic features that are characteristic of MDR have been described; these include (1) resistance to many structurally and functionally unrelated drugs that have different cellular targets and modes of action; (2) reversal of MDR by certain agents, including verapamil and cyclosporin A; and (3) reduced intracellular drug accumulation relative to that of drug-sensitive cells. In this report we show that the introduction and overexpression of the hamster pgp1 cDNA confers to otherwise drug-sensitive cells an MDR phenotype with these features. Moreover, pgp1 transfectants showed varying degrees of resistance to anthracycline analogues, indicating that structural analogues of commonly used anticancer agents are capable of circumventing drug resistance conferred by pgp.
在培养中生长的仓鼠细胞，可能像人类和小鼠细胞一样，在接触某些细胞毒性化疗药物时产生多药耐药性（MDR）。已经描述了几种MDR的表型特征；这些特征包括：（1）对许多结构和功能不相关、具有不同细胞靶点和作用方式的药物具有抗性；（2）某些药物（包括维拉帕米和环孢菌素A）可逆转MDR；（3）相对于药物敏感细胞，细胞内药物积累减少。在本报告中，我们表明仓鼠pgp1 cDNA的导入和过表达赋予原本对药物敏感的细胞具有这些特征的MDR表型。此外，pgp1转染细胞对蒽环类类似物表现出不同程度的抗性，表明常用抗癌药物的结构类似物能够规避pgp赋予的耐药性。
