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Effects of cyclosporin a and verapamil on the intracellular daunorubicin accumulation in chinese hamster ovary cells with increasing levels of drug‐resistance
Author(s) -
Silbermann M. H.,
Boersma A. W. M.,
Jamssen A. L. W.,
Scheper R. J.,
Herweijer H.,
Nooter K.
Publication year - 1989
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910440428
Subject(s) - daunorubicin , chinese hamster ovary cell , p glycoprotein , pharmacology , efflux , verapamil , multiple drug resistance , drug , drug resistance , flow cytometry , intracellular , biology , cell culture , chemistry , medicine , microbiology and biotechnology , immunology , biochemistry , leukemia , genetics , calcium
Multidrug‐resistance (MDR) is characterized by the presence of a 170 kDa glycoprotein (P‐glycoprotein) in the plasma membrane. P‐glycoprotein is thought to act as an efflux pump, leading to reduced drug accumulation in MDR cells. This defect in drug accumulation can be overcome by membrane transport modulating agents (MTMAs). We determined the concentration of MTMA needed for maximal restoration of daunorubicin content in 4 Chinese hamster ovary cell lines with increasing levels of drug‐resistance using flow cytometry. Stimulation of daunorubicin accumulation occurred in a dose‐dependent manner. The required level of MTMA needed for maximal drug accumulation increased with the level of drug‐resistance. CH r A3 cells, which have a level of resistance comparable to clinical samples, needed relatively low concentrations of MTMA for maximal restoration of drug accumulation. This indicates that, in trials combining drugs and MTMAs, low dosages of MTMAs could be sufficient for optimal potentiation of cytotoxicity.