Influence of fibroblast growth factor receptor antagonist BGJ398 in biological characteristics of gliomas
10.3760/cma.j.issn.1671-8925.2017.06.001
- VernacularTitle:成纤维细胞生长因子受体抑制剂BGJ398对胶质瘤生物学特性的影响
- Author:
Xiao LI
1
;
Yun WANG
;
Taoliang CHEN
;
Jiansheng CHEN
;
Min HUANG
;
Yajie CHI
;
Yuantao YANG
;
Yiquan KE
Author Information
1. 510282 广州,国家临床重点专科,教育部工程技术研究中心,广东省脑功能修复与再生重点实验室,南方医科大学珠江医院神经外科
- Keywords:
Glioma;
Fibroblast growth factor receptor;
BGJ398;
Tyrosine kinase inhibitor
- From:
Chinese Journal of Neuromedicine
2017;16(6):541-546
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of fibroblast growth factor receptor (FGFR) receptor antagonist BGJ398 in growth, migration and invasiveness of gliomas. Methods (1) Glioma cells U87 and U251 were routinely cultured in vitro and divided into BGJ398 treatment group (10 μmol/L BGJ398 complete medium) and control group; the proliferation of U87 and U251 cells was detected by CCK-8 and colony formation; 2 d after cultivation, the migration and invasion of U87 and U251 cells were measured by wound-healing assay and Transwell assay. The phosphor-FGFR (pFGFR) level and vimentin expressions were detected by Western blotting. (2) Eight BALB/c nude mice were performed abdominal subcutaneous injection of 200 μL U87 cells (1×107 cells) and randomly divided into BGJ398 treatment group (giving physiological saline solution containing 20 mg/kg BGJ398) and control group (giving physiological saline solution); 15 d after cultivation, the quality of the subcutaneously implanted tumors was compared between the two groups, and the vimentin expression was detected by Western blotting. Results (1) Three, 4 and 5 d after cultivation, the optical density in the U87 cells of BGJ398 treatment group was significantly lower than that in the control group (3 d: t=4.059, P=0.015; 4 d: t=9.892, P=0.001; 5 d: t=10.259, P=0.001); 2, 3, 4 and 5 d after cultivation, the optical density in the U251 cells of BGJ398 treatment group was significantly lower than that in the control group (2 d: t=3.780, P=0.019; 3 d: t=4.515, P=0.011; 4 d: t=16.205, P=0.000; 5 d: t=17.613, P=0.000); 10 d after cultivation, the cloning number of U87 and U251 cells in the BGJ398 treatment group was significantly smaller than that in the control group (P<0.05); the results of wound-healing assay showed that the migration of U87MG cells in the BGJ398 treatment group was significantly slower than that in the control group (P<0.05); 24 h after cultivation, the number of U87 cells migration in the BGJ398 treatment group was significantly smaller as compared with that in the control group (P<0.05); 48 h after cultivation, the number of U87 and U251 cells passed the pore membrane in the BGJ398 treatment group was significantly smaller as compared with that in the control group (P<0.05). Western blotting showed that the content of pFGFR and vimentin in U87 and U251 cells of the BGJ398 treatment group decreased significantly as compared with that in the control group (P<0.05). (2) The subcutaneous tumor tissues in the BGJ398 treatment group[(0.186± 0.064) g] were significantly smaller than those in the control group[(0.450±0.106) g] (P<0.05); Vimentin expression in the BGJ398 treatment group (2.503±0.359) was significantly decreased than that in the control group (4.125±1.155, P<0.05). Conclusion Experiments in vivo and in vitro confirm that BGJ398 can inhibit the activation of FGFR and the growth, migration, and invasion of glioma cells, indicating that FGFR is one of effective targets for the treatment of gliomas.
