Study on reversal effect of nilotinib in combination with 5-BrTet on multidrug resistance of K562/A02 cell line.
- Author:
Bao-An CHEN
1
;
Xue-Yun SHAN
;
Jian CHEN
;
Fei WANG
;
Jia-Hua DING
;
Chong GAO
;
Gang ZHAO
;
Xue-Mei WANG
;
Wen-Lin XU
;
Feng GAO
;
Guo-Hua XIA
;
Michael SCHMITT
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; metabolism; Daunorubicin; pharmacology; Drug Resistance, Multiple; drug effects; Drug Resistance, Neoplasm; drug effects; Humans; K562 Cells
- From: Chinese Journal of Hematology 2010;31(6):385-388
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the reversible effect of nilotinib, BrTet (5-bromotetrandrine) and their combination on multidrug resistance cell line K562/A02 and its mechanism.
METHODSCell proliferation inhibition was assessed by MTT method and cell apoptosis by flow cytometry (FCM). The expression of mdr1 mRNA was determined by RT-PCR, and the expression of P-gp was assessed by Western blot.
RESULTSAfter 48 h 5 nmol/L nilotinib or 0.5 µmol/L BrTet treatment, IC(50) of daunorubicin (DNR) to K562/A02 was 4.52 mg/L or 5.41 mg/L respectively; While on combinative treatment, its IC(50) decreased to 2.98 mg/L. Nilotinib or BrTet alone was not able to increase the DNR induced apoptosis rate of K562/A02 cell (P > 0.05), while on combination treatment the apoptosis rate increased remarkably. After 48 h 5 nmol/L nilotinib or 0.5 µmol/L BrTet treatment alone, gray-scale value of mdr1 mRNA was 0.48 ± 0.04 or 0.64 ± 0.01, respectively; while on combinative treatment the value decreased to 0.35 ± 0.04. The P-gp expression level in K562/A02 cells was 0.61 ± 0.05, or 0.52 ± 0.02 when treated with 5 nmol/L nilotinib or 0.5 µmol/L BrTet alone for 48 h, but on combination treatment, the level decreased to 0.44 ± 0.03.
CONCLUSIONNilotinib or BrTet alone can partially reverse drug resistance of K562/A02 cells. The mechanism may be associated with the decrease of mdr1 mRNA and P-gp expression and increase of the apoptosis rate. And there is a synergistic action with these two agants in combination.