Changes of the distribution and accumulation of adriamycin in the sensitive and multidrug-resistant HL-60 cells
- VernacularTitle:阿霉素在人白血病敏感细胞株HL-60和多药耐药细胞株HL-60/ADR的分布和积聚变化
- Author:
Lei WANG
;
Hong KE
;
Yiyu WANG
;
Dongming REN
;
Jie CUI
- Publication Type:Journal Article
- Keywords:
adriamycin;
flow cytometry;
confocal scanning laser microscope;
drug distribution;
multidrug resistance;
cell line;
HL-60/ADR
- From:
Chinese Pharmacological Bulletin
2003;0(12):-
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate subcellular distribution and accumulation of ADR in the sensitive and multidrug-resistant HL-60 cells and its relation to multidrug resistance.Methods The subcellular distribution and accumulation of ADR were studied by confocal scanning laser microscope and flow cytometry.The effects of verapamil,BSO,brefeldin A and chloroquine on ADR distribution and accumulation in HL-60/ADR cells were also examined.Rhodamine123,NBD-ceramide and neutral red were used as fluorescent probes to stain the mitochondria,Golgi apparatus and lysosomes respectively were used to identify the subcellular compartments where ADR was sequestered.Results In drug-sensitive cell line HL-60,ADR fluorescence distributed evenly in the nucleus and cytoplasm,while in multidrug-resistant cell line HL-60/ADR,ADR fluorescence distributed in a punctated pattern in the cytoplasm and was reduced in the nucleus.The mode of ADR distribution in HL-60/ADR cells is highly similar to that of NBD-ceramide.BSO and brefeldin A,instead of verapamil and chloroquine could reverse the abnormal distribution and accumulation of ADR in HL-60/ADR cells.Conclusions The change of ADR distribution and reduction of ADR accumulation in multidrug-resistant cell line was involved in the mechanism of multidrug resistance.
