CML cell apoptosis induced by AMN107 combined with heme oxygenase-1 inhibitor.
- Author:
Cheng CHEN
1
;
Ji-Shi WANG
;
Chang YNAG
;
Yan-Yan YU
;
Yan LI
;
Dan MA
;
Qin FANG
Author Information
1. Department of Hematology, Guiyang Medical College, Guiyang, Guizhou Province, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Heme Oxygenase-1;
antagonists & inhibitors;
Humans;
K562 Cells;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive;
pathology;
Protoporphyrins;
pharmacology;
Pyrimidines;
pharmacology
- From:
Journal of Experimental Hematology
2012;20(4):867-871
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the effect of AMN107 (nilotinib) combined with heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin IX (ZnPPIX) on chronic myeloid leukemia (CML) cells and its mechanism. Proliferative rate of cells treated with AMN107 (10 µmol/L) and ZnPPIX (10 µmol/L) alone or both for different time was observed by MTT and trypan blue methods; the expression of HO-1 in the control group, ZnPPIX (10 µmol/L) group, AMN107 (10 µmol/L) group, AMN107 (10 µmol/L) combined with ZnPPIX (10 µmol/L) group was evaluated by semi-quantitative RT-PCR and Western blot at 48 h. Cell apoptosis was detected by flow cytometry with Annexin V/PI double staining at 48 h. The results showed that the strongest inhibition of cell proliferation was detected in combined group, and in a time-dependent manner; the expression level of HO-1 was lowest in combined group; the cell apoptosis rates were (11.38 ± 0.02)%, (17.44 ± 0.08)%, (39.81 ± 0.07)% and (56.46 ± 0.19)% in the control group, ZnPPIX group, AMN107 group, AMN107 combined with ZnPPIX group at 48 h respectively. It is concluded that the second-generation tyrosine kinase inhibitor AMN107 can induce the apoptosis in CML cells. Inhibition of HO-1 expression can enhance the killing effect of AMN107 on CML cells, which provides experimental evidence to further improve the clinical efficacy of CML treatment.
