[Altered subcellular distribution of daunorubicin in the non-P-glycoprotein-mediated multidrug-resistant cell line HL-60/ADR].
OBJECTIVE
To investigate DNR subcellular distribution in the non-P-glycoprotein-mediated multidrug-resistant cell line HL-60/ADR and its relation to multidrug resistance.


METHODS
DNR subcellular disposition was studied by confocal scanning laser microscopy, fluorescent methods, MTT and RT-PCR. The effects of verapamil, brefeldin A, chloroquine were also examined.


RESULTS
In the drug-sensitive cell line HL-60 DNR fluorescence distributed evenly in the nucleus and cytoplasm, while in the resistant cell line DNR distributed in a punctate pattern in the cytoplasm and was reduced in the nucleus. Verapamil, brefeldin A, but not chloroquine could recover the intracellular distribution of DNR from punctate to even in the resistant cell line.


CONCLUSIONS
Altered subcellular disposition of DNR in resistant cell line was involved in the mechanism of multidrug resistance.
Gong
Y
Y
Renji Hospital, Shanghai Second Medical University, Shanghai 200021, China.
Wang
Y
Y
Chen
F
F
Han
J
J
Shao
N
N
Fang
Z
Z
Ouyang
R
R
D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003630:Daunorubicin / Q000493:pharmacokinetics* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D018922:HL-60 Cells; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D003630:Daunorubicin