Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors

被引：17

作者：

Davies, SL

Bergh, J

Harris, AL

Hickson, ID

机构：

[1] UNIV OXFORD,JOHN RADCLIFFE HOSP,INST MOL MED,IMPERIAL CANC RES FUND LABS,OXFORD OX3 9DU,ENGLAND

[2] UNIV UPPSALA,AKAD SJUKHUSET,DEPT ONCOL,S-75185 UPPSALA,SWEDEN

来源：

BRITISH JOURNAL OF CANCER | 1997年 / 75卷 / 06期

关键词：

topoisomerase II; drug resistance; ICRF-159; multidrug resistance-related protein; multidrug resistance;

D O I：

10.1038/bjc.1997.146

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We have studied the relationship between expression of genes implicated in mediating resistance to cleavable complex-forming topoisomerase II (topo II) inhibitors and cellular sensitivity to ICRF-159, a 'catalytic' inhibitor of topo II. Overexpression of the membrane transporters, P-glycoprotein and multidrug resistance-related protein (MRP), or down-regulation of topo II alpha and/or -beta, did not confer ICRF-159 resistance. Indeed, marked topo II alpha down-regulation appeared to be associated with collateral sensitivity to ICRF-159. Our results indicate that the resistance mechanisms that pertain to cleavable complex-forming topo II inhibitors and ICRF-159 are distinct. The evidence presented here suggests that topo II alpha, not topo II beta, is mote likely to be the major in vivo target for ICRF-159.

引用

页码：816 / 821

页数：6

共 26 条

[1]

Ausubel FM., 1994, Curr. Protoc. Mol. Biol

[2]

BATIST G, 1986, J BIOL CHEM, V261, P5544

[3]

BECK WT, 1993, ADV ENZYME REGUL, V33, P113

[4] P-GLYCOPROTEIN, MULTIDRUG-RESISTANCE AND TUMOR PROGRESSION [J].