Effect of intracellular acidification on P-glycoprotein in drug-resistant K562/A02 cells.
- Author:
Ying LU
1
;
Qing-Hua LI
;
Li MA
;
Bin LI
;
Wen-Su YUAN
;
Yong-Xin RU
;
Jian-Xiang WANG
;
Tian-Xiang PANG
Author Information
1. National Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter, Sub-Family B;
ATP-Binding Cassette, Sub-Family B, Member 1;
metabolism;
Drug Resistance, Multiple;
Drug Resistance, Neoplasm;
Humans;
Hydrogen-Ion Concentration;
K562 Cells
- From:
Journal of Experimental Hematology
2009;17(3):568-573
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study was to investigate the effect of intracellular acidification on the P-gp in K562/A02 cells. Confocal laser microscope was used to determine the intracellular acidification. MTT assay was used to detect the cytotoxicity of intracellular acidification on K562 and K562/A02 cells. Flow cytometry was applied to measure the influence of intracellular acidification on the activity of P-gp. The P-gp expression at protein and mRNA levels were determined by Western blot and real-time RT-PCR respectively. The results indicated that intracellular acidification had no obvious cytotoxicity on K562 and K562/A02 cells. The function of P-gp in K562/A02 cells weakened along with decrease of intracellular acidification, the intracellular acidification significantly increased the accumulation of Rhodamine 123 (Rh 123) and suppressed the efflux of Rh 123 mediated by P-gp. The intracellular acidification also inhibited the expression of P-gp in K562/A02 cells at protein and mRNA levels which showed intracellular acidification with time-dependence. It is concluded that the intracellular acidification can inhibit the expression and function of P-gp in K562/A02 cells.
