Inducing apoptosis and reversal effect of nilotinib in combination with tetrandrine on multidrug resistance of K562/A02 cell line.
- Author:
Ting-Yun CUI
1
;
Bao-An CHEN
;
Jia-Hua DING
;
Chong GAO
;
Jian CHENG
;
Wen BAO
;
Yue-Jiao ZHONG
;
Xue-Yun SHAN
;
Feng GAO
;
Guo-Hua XIA
;
Anita SCHMITT
;
Michael SCHMITT
Author Information
1. Department of Hematolagy, Zhongda Hospital, Southeast University Medical College, Nanjing 210009, Jiangsu Province, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Benzylisoquinolines;
administration & dosage;
pharmacology;
Daunorubicin;
pharmacology;
Drug Resistance, Multiple;
Drug Resistance, Neoplasm;
Gene Expression Regulation, Leukemic;
Humans;
Inhibitor of Apoptosis Proteins;
genetics;
K562 Cells;
Pyrimidines;
administration & dosage;
pharmacology;
bcl-2-Associated X Protein;
genetics
- From:
Journal of Experimental Hematology
2011;19(1):28-33
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the relevance of nilotinib in combination with tetrandrine (Tet) on reversing multidrug resistance and inducing apoptosis of K562/A02 cell line and its mechanism. Methyl-thiazol tetrazolium (MTT) assay was employed to examine the pharmacological effect of nilotinib or Tet alone on K562/A02 cell line, the IC(50) of daunorubicin (DNR) on K562/A02 cell line treated with nilotinib and Tet was calculated; the flow cytometry (FCM) was employed to detect the apoptosis rate of K562/A02. The expression of bax/survivin mRNA was determined by RT-PCR, and the expression of bax/survivin protein was assayed by Western blot. The results showed that after being treated by 5 nmol/L nilotinib or 1.0 µml/L Tet for 48 hours, IC(50) of DNR to K562/A02 was 5.71 ± 0.72 mg/L or 6.52 ± 0.43 mg/L, respectively, while in their combined treatment, IC(50) decreased to 3.12 ± 0.13 mg/L. Nilotinib or Tet alone could increase DNR-inducing apoptosis rate of K562/A02 cell, while the apoptosis rate of K562/A02 increased remarkably in combination treatment of nilotinib with Tet. After being treated with 5 nmol/L nilotinib or 1.0 µml/L Tet alone for 48 hours, the expressions of bax mRNA and BAX protein was up-regulated, while both effects were more obvious in combination treatment of nilotinib with Tet. Treatment with 5 nmol/L nilotinib or 1.0 µmol/L Tet alone for 48 hours down-regulated the expression of survivin mRNA and its protein, while treatment of nilotinib in combination with Tet had more significant effect on down-regulation of their expression. It is concluded that the K562/A02 cells are resistant to DNR, nilotinib or Tet alone both can partially reverse resistance of K562/A02 cells to DNR, increase the apoptosis rate of K562/A02 cells. Combination of nilotinib with Tet shows obvious synergistic action, mechanism of which may associate with up-regulation of bax mRNA and BAX protein expressions and down-regulation of survivin mRNA and its protein expressions.
