CML cell apoptosis induced by AMN107 combined with heme oxygenase-1 inhibitor / 中国实验血液学杂志
Journal of Experimental Hematology
;
(6): 867-871, 2012.
Article
in Chinese
| WPRIM
| ID: wpr-278476
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Protoporphyrins
/
Pyrimidines
/
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/
Apoptosis
/
K562 Cells
/
Heme Oxygenase-1
Limits:
Humans
Language:
Chinese
Journal:
Journal of Experimental Hematology
Year:
2012
Type:
Article
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