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.
Conclusion: Altered subcellular disposition of DNR in resistant cell line was involved in the mechanism of multidrug resistance.