Reversal effect of gambogic acid on multidrug resistance of K562/A02 cell line.
- Author:
Liang TIAN
1
;
Juan LIU
;
Bao-An CHEN
;
Jian CHENG
;
Jia-Hua DING
;
Shuai WANG
;
Guo-Hua XIA
;
Feng GAO
;
Ze-Ye SHAO
;
Hai-Jun ZHANG
;
Qing-Long GUO
;
Hai-Wei ZHANG
;
Lei WANG
;
Yan-Yan REN
;
Xiao-Hui CAI
;
Ran LIU
Author Information
1. Department of Hematology and Oncology, Southeast University Clinical Medical College, Nanjing, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Doxorubicin;
pharmacology;
Drug Resistance, Multiple;
drug effects;
Drug Resistance, Neoplasm;
drug effects;
Gene Expression Regulation, Leukemic;
Humans;
Inhibitor of Apoptosis Proteins;
metabolism;
K562 Cells;
Substance P;
metabolism;
Xanthones;
pharmacology
- From:
Journal of Experimental Hematology
2012;20(2):252-257
- CountryChina
- Language:Chinese
-
Abstract:
This study was purposed to investigate the reversal effect of gambogic acid (GA) on multidrug resistance of K562/A02 cells and its mechanism. The IC(50) (half maximal inhibitory concentration) of adriamycin (ADM) was evaluated by MTT. Cell apoptosis was detected by flow cytometry. Morphological changes of K562/A02 cells were observed by fluorescent microscopy with DAPI staining. The expressions of Survivin and P-gp were determined by Western blot. The results showed that the IC(50) of ADM on K562 and K562/A02 cell proliferation were (1.42 ± 0.07) µg/ml and (28.42 ± 1.40) µg/ml respectively. GA ≤ 0.0625 µmol/L had no inhibitory effect on proliferation of K562 and K562/A02. 0.0625 µmol/L GA could enhance the sensitivity of K562/A02 cells to ADM (P < 0.05) and the reversal multiples was 1.53. The apoptotic rate was raised after treating with ADM combined with 0.0625 µmol/L GA for 48 h (P < 0.05). Morphological differences were typical and obvious between cells of control and treated groups under fluorescence microscopy using DAPI staining. After treating K562/A02 cells with ADM combined with 0.0625 µmol/L GA for 48 h, the expressions of Survivin and P-gp were down-regulated at protein levels. It is concluded that GA can enhance the sensitivity of K562/A02 cells to ADM, which may be related to increasing cell apoptosis and down-regulating expressions of Survivin and P-gp.
