Effect of cyclosporine A, raloxifene and their combination on the reversion of multidrug resistance of K562/A02 line.
- Author:
Wen BAO
1
;
Bao-An CHEN
;
Feng GAO
;
Jia-Hua DING
;
Wen-Lin XU
;
Hui-Ling SHENG
;
Chong GAO
;
Yun-Yu SUN
;
Jian CHEN
;
Jun WANG
;
Gang ZHAO
;
Yan MA
Author Information
1. Department of Hematology, Zhongda Hospital, Clinical medical college of Southeast University, Nanjing 210009, China.
- Publication Type:Journal Article
- MeSH:
ATP-Binding Cassette, Sub-Family B, Member 1;
biosynthesis;
drug effects;
genetics;
Cyclosporine;
pharmacology;
Doxorubicin;
pharmacology;
Drug Resistance, Multiple;
drug effects;
Drug Resistance, Neoplasm;
drug effects;
Drug Synergism;
Humans;
K562 Cells;
drug effects;
pathology;
RNA, Messenger;
biosynthesis;
drug effects;
genetics;
Raloxifene Hydrochloride;
pharmacology
- From:
Journal of Experimental Hematology
2006;14(5):895-899
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the reversible effect of cyclosporine A, raloxifene and their combination on multidrug resistance cell line K562/A02. The IC(50) (the concentration causing 50% inhibition of cell growth) of DNR were assayed by MTT method, the expression level of mdr-1 mRNA was assayed by RT-PCR, p-glycoprotein (P-gp) expression and intracellular DNR concentration were detected by flow cytometry. The results showed that the IC(50) of DNR on K562/A02 and K562 cells were 23.51 mg/L and 0.29 mg/L, respectively. The IC(50) of DNR on K562/A02 cells in treatment with raloxifene CsA and both combination were 5.98, 8.15 and 3.68 mg/L respectively, but both drugs not influenced IC(50) of DNR on K562 cells. Pretreating K562/A02 cells with raloxifene (2.5 mg/L) or CsA (1 mg/L) for 48 hours partially restored the sensitivity of K562/A02 cells to DNR. Cyclosporine A and raloxifene (alone or combination) elevated the intracellular DNR concentration in K562/A02, down regulated P-gp and mdr-1 mRNA expressions. It is concluded that multidrug resistance (MDR) can be partially reversed by CsA or raloxifene, the combination of both drugs shows a great synergistic reversal effect.
