Reversal of multidrug-resistance in human leukemia cell line K562/A02 by tyrosine kinase inhibitors.
- Author:
Xue-Yun SHAN
1
;
Bao-An CHEN
;
Guo-Hua XIA
;
Wen-Lin XU
;
Jia-Hua DING
;
Chong GAO
;
Yun-Yu SUN
;
Jun WANG
;
Jian CHENG
;
Gang ZHAO
;
Wen BAO
;
Hui-Hui SONG
;
Feng GAO
;
Fei WANG
;
Xue-Mei WANG
Author Information
1. Department of Hematology, Zhongda Hospital, Southeast University Clinical Medical College, Nanjing 210009, Jiangsu Province, China.
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter, Sub-Family B;
ATP-Binding Cassette, Sub-Family B, Member 1;
metabolism;
Benzamides;
Daunorubicin;
pharmacology;
Doxorubicin;
pharmacology;
Drug Resistance, Multiple;
drug effects;
Drug Resistance, Neoplasm;
drug effects;
Humans;
Imatinib Mesylate;
K562 Cells;
Piperazines;
pharmacology;
Protein Kinase Inhibitors;
pharmacology;
Pyrimidines;
pharmacology
- From:
Journal of Experimental Hematology
2010;18(1):90-95
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the reversal effect of tyrosine kinase inhibitors (TKI) Imatinib and Nilotinib on multidrug-resistant cell line K562/A02. The expression levels of mdr-1 mRNA and bcr-abl mRNA were assayed by RT-PCR. The protein levels of P-glycoprotein (P-gp) and P210 were detected by Western blot. The daunorubicin (DNR) accumulation in K562/A02 cells were analyzed by flow cytometry (FCM). The results showed that the 0.0625 micromol/L Imatinib or 5 nmol/L Nilotinib alone had no cytotoxic effect on the inhibition of K562/A02 cells. When K562/A02 cells were treated with Imatinib or Nilotinib alone for 48 hours, the expressions of mdr-1 mRNA, der/abl mRNA, P-gp and P210 protein were all down-regulated, furthermore the effect of Nilotinib was stronger than that of Imatinib. The detection of fluorescence intensity revealed that the DNR concentration in K562/A02 cells treated with Imatinib or Nilotinib alone for 48 hours were 7.85% and 12.02% of K562 cells respectively. It is concluded that the tyrosine kinase inhibitors show great effect reversing drug resistance of cells, moreover, the effect of Nilotinib is stronger than that of Imatinib.
