GENISTEIN MODULATES THE DECREASED DRUG ACCUMULATION IN NON-P-GLYCOPROTEIN MEDIATED MULTIDRUG-RESISTANT TUMOR-CELLS

被引：154

作者：

VERSANTVOORT, CHM ^{[1
]}

SCHUURHUIS, GJ ^{[1
]}

PINEDO, HM ^{[1
]}

EEKMAN, CA ^{[1
]}

KUIPER, CM ^{[1
]}

LANKELMA, J ^{[1
]}

BROXTERMAN, HJ ^{[1
]}

机构：

[1] FREE UNIV AMSTERDAM HOSP,DEPT MED ONCOL,BR 232,BOELELAAN 1117,1081 HV AMSTERDAM,NETHERLANDS

来源：

BRITISH JOURNAL OF CANCER | 1993年 / 68卷 / 05期

关键词：

D O I：

10.1038/bjc.1993.458

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In tumour cells the pharmacological basis for multidrug resistance (MDR) often appears to be a reduced cellular Cytostatic drug accumulation caused by the drug efflux protein, P-glycoprotein (Pgp MDR), or by other drug transporters (non-Pgp MDR). Here we report the reversal of the decreased daunorubicin (DNR) accumulation in five non-Pgp MDR cell lines (GLC4/ADR, SW-1573/2R120, HT1080/DR4, MCF7/Mitox and HL60/ADR) by genistein. Genistein inhibited the enhanced DNR efflux in the GLC4/ADR cells. In these cells the decreased VP-16 accumulation was also reversed by genistein. Three other (iso)flavonoids biochanin A, apigenin and quercetin also increased the DNR accumulation in the GLC4/ADR cells. In contrast to the effects on non-Pgp MDR cells, 200 mum genistein did not increase the reduced DNR accumulation in three Pgp MDR cell lines (SW-1573/2R160, MCF7/DOX40 and KB8-5) or in the parental cell lines. In conclusion the use of genistein provides a means to probe non-Pgp related drug accumulation defects.

引用

页码：939 / 946

页数：8

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