Isoalantolactone suppresses proliferation of chronic myelogenous leukemia drug-resistant cell line K562/A02 through bcr-abl-STAT5 signaling pathway
10.3760/cma.j.issn.1009-9921.2017.07.001
- VernacularTitle:异土木香内酯通过bcr-abl-STAT5信号通路抑制慢性粒细胞白血病耐药细胞K562/A02增殖
- Author:
Hong CAI
;
Chunhui YANG
- Keywords:
Leukemia;
myeloid;
chronic;
Apoptosis;
Cell cycle;
Isoalantolactone
- From:
Journal of Leukemia & Lymphoma
2017;26(7):385-389
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of isoalantolactone on the proliferation of human chronic myelogenous leukemia drug-resistant cell line K562/A02. Methods K562/A02 cells were treated with 6.25, 12.5, 25, 50 and 100 μmol/L isoalantolactone for 24 and 48 h, cell viability was analyzed with MMT assay. K562/A02 cells were treated with 10, 15, 20 μmol/L isoalantolactone for 24 h. Flow cytometry was used to examine the effect of isoalantolactone on the cell-cycle and apoptosis of K562/A02 cells. The related proteins were analyzed using Western blot. One-way ANOVA was used for statistical analysis. Results Isoalantolactone effectively inhibited the proliferation of K562/A02 cells in a dose-dependent manner (P<0.05) with IC50 value of (15.00 ±1.03) μmol/L at 24 h, respectively; Flow cytometry displayed that isoalantolactone may induce K562/A02 cells apoptosis in a concentration-dependent manner (P<0.05). The apoptotic rate significantly increased from (2.71 ±0.52) % in the control group to (19.10 ±1.55) %, (27.61 ± 2.32)%and (32.01±3.01)%(F=33.901, P<0.05), respectively, after treatment with 10, 15, and 20 μmol/L of isoalantolactone for 24 h. The percentage of cells in the S phase increased from (57.80±2.11) % to (68.62± 2.89)%, (78.41±3.51)%and (80.61±2.90)%, respectively (F=51.328, P<0.05). Western blot indicated that the expression of bcl-2, p-bcr-abl, p-STAT5, CDK2 and cyclin A significantly decreased (P< 0.05), and that of cytochrome C, Bax, and p21 increased with the increasing of isoalantolactone concentration (P< 0.05). Conclusion Isoalantolactone can significantly inhibit the proliferation of K562/A02 cells through bcr-abl-STAT5 signaling pathway.
