Apoptosis of KBM5R cell line with T315I point mutation induced by arsenic trioxide.
- Author:
Xiao-Feng LI
1
;
Jing-He LI
;
Chun-Hong WANG
;
Xiu-Li WANG
;
Qiu-Ju LIU
;
Wen XU
;
Bo JIA
;
Lin QIU
;
Jun MA
Author Information
1. Department of Oncology & Hematology, Jilin University Second Hospital, Changchun 130041, Jilin Province, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Arsenicals;
pharmacology;
Benzamides;
Caspase 3;
metabolism;
Caspase 8;
metabolism;
Caspase 9;
metabolism;
Cell Line, Tumor;
Drug Resistance, Neoplasm;
genetics;
Flow Cytometry;
Humans;
Imatinib Mesylate;
Oxides;
pharmacology;
Piperazines;
pharmacology;
Point Mutation;
Pyrimidines;
pharmacology
- From:
Journal of Experimental Hematology
2011;19(3):643-647
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the inducing-apoptosis effect of arsenic trioxide (ATO) on imatinib (IM)-resistant chronic myeloid leukemia (CML) cell line KBM5R with T315I point mutation. CML cell line KBM5R with T315I point mutation and wild-type cell line KBM5 were selected for study. Resistance of KBM5R cells to IM and proliferation of KBM5 and KBM5R cells treated with ATO were detected by MTT; apoptosis of KBM5 and KBM5R cells were quantified by flow cytometry; the expression of apoptosis-related protein caspase-3, -8, -9 was determined by Western blot. The results showed that (1) IC(50) of KBM5R and KBM5 cells treated with IM were 12.66 ± 0.565 µmol/L and 0.303 ± 0.031 µmol/L respectively, and significantly different from each other. (2) the proliferation of KBM5 and KBM5R cells treated with different concentrations of ATO was inhibited in dose- and time-dependent manners at 24, 48, 72, 96 hours, and inhibition of KBM5R cell proliferation was stronger than KBM5 in the same drug concentration and time. (3) the apoptosis rate of KBM5 and KBM5R cells treated with 2, 4, 8 µmol/L ATO for 48 hours increased in a concentration-dependent manner, and the apoptosis rate of KBM5R was higher than that of KBM5 cells in the same drug concentration. (4) the expression of cleaved caspase-3, -8, -9 protein in KBM5 and KBM5R cells treated with 4 µmol/L ATO for 24 hours significantly increased. It is concluded that KBM5R cells are significantly resistant to IM; ATO can inhibit the proliferation and induce the apoptosis of KBM5R and KBM5 cells. As compared with wild-type KBM5 cells, effect of ATO on inhibition of proliferation and induction of apoptosis in KBM5R cells are more stronger. ATO can induce the apoptosis of KBM5 and KBM5R cells through the activation of apoptosis-related caspase-3, -8, -9 protein.
