CIRCUMVENTION OF CONFLUENCE-DEPENDENT RESISTANCE IN A HUMAN MULTI-DRUG-RESISTANT COLON-CANCER CELL-LINE

被引：24

作者：

GARRIDO, C ^{[1
]}

CHAUFFERT, B ^{[1
]}

PINARD, D ^{[1
]}

TIBAUT, F ^{[1
]}

GENNE, P ^{[1
]}

ASSEM, M ^{[1
]}

DIMANCHEBOITREL, MT ^{[1
]}

机构：

[1] FAC MED DIJON,ONCOHEMATOL LAB,F-21033 DIJON,FRANCE

来源：

INTERNATIONAL JOURNAL OF CANCER | 1995年 / 61卷 / 06期

关键词：

D O I：

10.1002/ijc.2910610621

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Colorectal adenocarcinomas are inherently resistant to anthracyclines and other topoisomerase-II inhibitors. Resistance to doxorubicin of colon cancer cells (Caco2) depends on 2 main mechanisms. The first is typical multi-drug resistance, characterized by the mdr1 gene and its product the P170 membrane glycoprotein. P170 effluxes anthracyclines out of cancer cells and is antagonized in vitro by verapamil. The second mechanism, which develops when cell-culture density increases, we have designated confluence-dependent resistance. Confluence-dependent resistance depends on the reduced topoisomerase II content of the G(0)/G(1)-phase cells which accumulate in the confluent population. We show here that short treatments of confluent Caco2 cells with slightly toxic concentrations of DNA-damaging agents (cisplatin, melphalan or mitomycin C) produced a transient accumulation of cells in S- and G(2)/M-phases of the cell cycle. Concomitantly with the increase in the S-phase population, the topoisomerase II cellular level and the sensitivity of cells to doxorubicin were greatly enhanced. Overcoming confluence-dependent resistance through S-phase accumulation and inhibition of multi-drug resistance by verapamil were fully additive, and a nearly complete reversal of confluent Caco2 cells' resistance to doxorubicin was obtained when both strategies were combined. (C) 1995 Wiley-Liss, Inc.

引用

页码：873 / 879

页数：7

共 22 条

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