Rapid development of glutathione-S-transferase-dependent drug resistance in vitro and its prevention by ethacrynic acid

被引：19

作者：

Caffrey, PB ^{[1
]}

Zhu, M ^{[1
]}

Zhang, YX ^{[1
]}

Chinen, N ^{[1
]}

Frenkel, GD ^{[1
]}

机构：

[1] Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA

来源：

CANCER LETTERS | 1999年 / 136卷 / 01期

关键词：

ovarian tumor cells; melphalan; drug resistance; glutathione-S-transferase; ethacrynic acid;

D O I：

10.1016/S0304-3835(98)00307-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Exposure of A2780 human ovarian tumor cells to a low concentration of melphalan in vitro for 7 days resulted in the development of melphalan resistance. This resistance was not a stable characteristic of the cells since it was lost after 2 weeks in culture in the absence of drug. The melphalan-resistant cells exhibited significant cross-resistance to cisplatin but only minor cross-resistance to doxorubicin. The resistant cells had elevated levels of glutathione-S-transferase activity and mRNA. Exposure of the cells to the ethacrynic acid resulted in a decrease in enzyme activity as well as a reversal of their drug-resistant phenotype, indicating that the enzyme is involved in the resistance. When ethacrynic acid was present during the 7-day exposure of the cells to melphalan, the development of drug resistance was prevented. This system may serve as a useful preliminary step in screening for agents which can prevent the development of chemotherapy-induced drug resistance in human cancer. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.

引用

页码：47 / 52

页数：6

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