Abstract The
purpose of this study was to determine what proportion of drug
resistance of MDRcell variant K562 / Dox was attributed to the
reduced steady state intracellular drug accumula-tion related to
overexpression of P-glycoprotein. K 562 / Dox was derived from
repeated expo-sure of human ervthroleukaemic cell line K562 cell to
doxorubicin. As assessed with MTTassay, the resistance of K 562/Dox
to 7 cytotoxic drugs increased variably in the range between1200 and
11 folds,K562 / Dox cells were positively stained with anti-human
p-glycoproteinmonoclonal antibody JSB-1, indicating overexpression of
P-gp. Intracellular drug accumula-tion in K562 / Dox,though
significantly reduced as compured with that in K562 cells,
wasmaximally restored by concurrent exposure of cells to 6 μmol / L
verapamil and 1.72 μmol / Leither of the doxorubicin,epirubicin or
daunorubicin..Similar results were obtained by exposureof cells to 12
μmol / L verapamil and 8.62 μmol/L drug, indicating that
restoration ofintracellular drug accumulation in MDR cells was
dependent on the relative concentrations ofverapamil to drug.
However,the resistances of K562/Dox cells to epirubicin and
daunorubicinstill remained for about 5.6 and > 6.6
folds,respectively, even at verapamil concentration of 6μmol / L,
suggesting at least a relatively big fraction of drug resistance was
not directly relatedto the altered cellular pharmacokinetics
associated with overexpression of P-glycoprotein.