Pim-1 kinase inhibitor SMI-4a inhibits proliferation and induces apoptosis in U937 cells
10.3969/j.issn.1000-4718.2017.09.015
- VernacularTitle:Pim-1激酶抑制剂SMI-4a抑制U937细胞增殖并诱导凋亡
- Author:
fang Rui FAN
1
;
yuan Li ZOU
;
lan Xiu HAO
;
mei Pei LU
;
rong Jun ZENG
;
lan Dong CAI
;
fu Xiang LIU
Author Information
1. 中山大学附属第三医院预防保健科
- Keywords:
Pim-1 kinase;
SMI-4a;
Acute myeloid leukemia;
Apoptosis
- From:
Chinese Journal of Pathophysiology
2017;33(9):1625-1630
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To study the growth-inhibiting and proapoptotic effects of Pim-1 kinase inhibitor SMI-4a on human acute myeloid leukemia cell line U937.METHODS:The effect of SMI-4a on U937 cell viability was measured by CCK-8 assay.The apoptotic rate was assessed by flow cytometry with Annexin V-PI staining and by fluorescence microscopy with Hoechst 33342 staining.Methylcellulose was used to assess colony formation ability of the cells.The expression of β-catenin in the cell cytosol and nucleus was detected by Western blot,and the expression of apoptosis-related proteins in the U937 cells was also examined.Intracellular distribution of β-catenin was detected by the method of immunofluorescence.RESULTS:SMI-4a inhibited the viability of U937 cells.Annexin V-PI staining showed that SMI-4a induced apoptosis in dose-and time-dependent manners.Hoechst 33342 staining also verified the apoptosis.SMI-4a significantly inhibited the colony formation capacity of the U937 cells.The results of Western blot demonstrated that SMI-4a upregulated the expression of PARP and Bax,downregulated the expression of Bcl-2 and change the distribution of β-catenin in intracellular compartment.Immunofluorescence observation found that SMI-4a decreased the expression level of β-catenin in the U937 cells.CONCLUSION:SMI-4a induces U937 cell apoptosis through regulating the expression of apoptosis-related genes.
