Inhibitory Eefects of the novel tyrosine kinase inhibitor BGJ398 against human leukemic cell line KG-1 cells.
10.3760/cma.j.issn.0253-2727.2018.02.013
- Author:
Yu JIANG
1
;
Hong Ying CHAO
1
;
Xiu Wen ZHANG
;
Min ZHOU
;
Xu Zhang LU
;
Ri ZHANG
;
Chuan HE
;
Qian WANG
Author Information
1. Department of Hematology, Affiliated Changzhou Second Hospital of Nanjing Medical University, Changzhou 213003, China.
- Publication Type:Journal Article
- Keywords:
8p11 myeloproliferative syndrome;
FGFR1;
KG-1 cells;
Tyrosine kinase inhibitor BGJ398
- MeSH:
Apoptosis;
Caspase 3;
Cell Line, Tumor;
Cell Proliferation;
Humans;
Phenylurea Compounds/pharmacology*;
Protein Kinase Inhibitors/pharmacology*;
Pyrimidines/pharmacology*
- From:
Chinese Journal of Hematology
2018;39(2):143-147
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the effects and possible mechanisms of the novel pan-FGFR inhibitor BGJ398 on KG-1 cells in vitro. Methods: Effects of BGJ398 on cells proliferation were detected by CCK-8, the apoptosis was assessed by Annexin V-FITC. Reverse transcriptionquantitative polymerase chain reaction (q-PCR) analysis was used to detect the expression of apoptosis-related genes B cell lymphoma-2 (Bcl-2) and caspase-3. Western blotting analysis was performed to explore the proteins expression levels of Bcl-2, caspase-3 and the expression of p-AKT, p-S6K, p-ERK and FGFR1. Results: BGJ398 effectively inhibited cell proliferation by dose-dependent manners. BGJ398(1.4 µmol/L) induced apoptosis of KG-1 cells by 36.4%, compared with 4.5% in the control group(P<0.001). Treatment with BGJ398 at 1.4 µmol/L led to significant increases in the expression levels of caspase-3, and decreases in the expression of Bcl-2 (P<0.005). In accordance with these results, Western blot analysis further confirmed the increased expression of Bcl-2 protein along with elevated caspase-3 activity. In addition, BGJ398 markedly down-regulated FGFR1OP2-FGFR1 fusion protein, p-AKT and p-S6K expression, but not p-ERK expression. Conclusion: Novel pan-FGFR inhibitor BGJ398 substantially suppressed KG-1 cell growth and induced apoptosis by inhibiting the expression of FGFR1, p-AKT, p-S6K and regulating apoptosis-related proteins.
