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The specific bisindolylmaleimide PKC-inhibitor GF 109203X efficiently modulates MRP-associated multiple drug resistance.

Abstract：

:The newly identified drug transporter MRP is functionally linked to a multiple drug resistance independent from P-glycoprotein. Resistance modifiers for this type of MDR are rare at present. We analyzed the modulating effect of the highly selective bisindolylmaleimide PKC inhibitor GF 109203X on the MRP overexpressing human MDR sublines HL60/AR and GLC4/ADR. Applying a 72 hour MTT-assay we demonstrate a complete reversal of the vincristine resistance of HL60/AR cells. Adriamycin resistance of HL60/AR, or vincristine resistance of GLC4/ADR were partially reversed. Furthermore, rhodamine 123 efflux from HL60/AR was strongly modulated by GF 109203X. Since the PKC inhibitor did not significantly influence MRP gene expression at the mRNA level which was examined by cDNA-PCR, our results suggest either a direct interaction of the compound with MRP or/and an indirect influence on MRP activity via altering the phosphorylation status of the transporter.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Gekeler V,Boer R,Ise W,Sanders KH,Schächtele C,Beck J

doi

10.1006/bbrc.1995.1017

subject

Has Abstract

pub_date

1995-01-05 00:00:00

pages

119-26

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(85)71017-0

journal_volume

206

pub_type

杂志文章

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