Effect of tyrosine kinase inhibitor Imatinib mesylate on proliferation, differentiation and apoptosis of Kasumi-1 leukemia cell line.
- Author:
Li-Hong WANG
1
;
Qing RAO
;
Min WANG
;
Jian-Xiang WANG
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; drug effects; genetics; Benzamides; Cell Differentiation; drug effects; genetics; Cell Line, Tumor; Cell Proliferation; drug effects; Humans; Imatinib Mesylate; Mutation; Piperazines; pharmacology; Protein-Tyrosine Kinases; antagonists & inhibitors; Proto-Oncogene Proteins c-kit; genetics; metabolism; Pyrimidines; pharmacology
- From: Chinese Journal of Hematology 2005;26(8):449-452
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the effect of Imatinib mesylate on proliferation, differentiation and apoptosis of leukemic Kasumi-1 cells bearing c-kit mutation.
METHODSKasumi-1 cells were treated with Imatinib at different concentrations in culture. Cell proliferation was assayed by MTT assay, expressions of c-kit antigen, surface myeloid antigen and cell cycle by flow cytometry, cell apoptosis by annexin V staining and agarose gel electrophoresis. Western blot was used to analyze the level of c-kit protein tyrosine phosphorylation.
RESULTSImatinib treatment caused a time- and dose-dependent inhibition of the cell proliferation, with a 72 h IC50 of 4.45 micromol/L. Imatinib treatment induced a decrease in the mean fluorescence value of c-kit antigen, a progressive decline in S-phase cell fraction and an increase in G0/G1 cells. Treatment with 5.00 micromol/L of imatinib for 72 h induced an increase in expression of myeloid surface protein CD11, CD13 and CD15, and for 24 h induced an increase in early apoptosis cells [from 9.04% to 86.84% (P < 0.05)]. The apoptosis ladder was observed on agarose gel electrophoresis on 5-day treatment. Tyrosine phosphorylation level of c-kit protein was decreased by Imatinib treatment.
CONCLUSIONTyrosine kinase inhibitor Imatinib mesylate treatment could inhibit proliferation of Kasumi-1 cells which bear a c-kit mutation, induce differentiation, apoptosis and G0/G1 cells accumulation.