Back to Search
Start Over
BLU-554, A selective inhibitor of FGFR4, exhibits anti-tumour activity against gastric cancer in vitro.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2022 Mar 05; Vol. 595, pp. 22-27. Date of Electronic Publication: 2022 Jan 21. - Publication Year :
- 2022
-
Abstract
- Background: Fibroblast growth factor receptor 4 (FGFR4) plays a key role in cancer progression, including tumour proliferation, invasion, and metastasis. Recent studies have shown that the FGFR4 selective inhibitor BLU-554 has clinical benefits on tumour regression in hepatocellular carcinoma patients. However, the effect of BLU-554 on gastric cancer remains unknown.<br />Methods: Changes in cell proliferation, apoptosis and cell cycle, migration, and invasion capabilities of MKN-45 cells treated with FGFR4 selective inhibitors were detected by CCK-8 assay, flow cytometry, transwell assay, and wound healing assay, respectively. Western blotting was used to detect the effect of BLU-554 on the expression of FGFR4, FRS2α, and p-ERK1/2.<br />Results: As the concentration of the inhibitor increased, the survival rate of gastric cancer cells decreased, and the trend of BLU-554 was more obvious; a high dose of BLU-554 caused significant cell apoptosis and cell cycle arrest as well as reduced cell invasion ability. The expression levels of FGFR4, FRS2α, and p-ERK1/2 were also significantly reduced when cells were treated with medium and high doses of BLU-554.<br />Conclusion: BLU-554 inhibited the mitogen-activated protein kinase (RAS-RAF-MEK-ERK) pathway by inhibiting FGFR4, ultimately impeding the proliferation and invasion of gastric cancer cells and promoting cell apoptosis and cell cycle arrest.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Antineoplastic Agents pharmacology
Cell Line, Tumor
Cell Survival drug effects
Dose-Response Relationship, Drug
Flow Cytometry
Humans
MAP Kinase Signaling System drug effects
Membrane Proteins metabolism
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Receptor, Fibroblast Growth Factor, Type 4 metabolism
Stomach Neoplasms pathology
Apoptosis drug effects
Cell Cycle Checkpoints drug effects
Cell Proliferation drug effects
Pyrans pharmacology
Quinazolines pharmacology
Receptor, Fibroblast Growth Factor, Type 4 antagonists & inhibitors
Stomach Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 595
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 35093636
- Full Text :
- https://doi.org/10.1016/j.bbrc.2022.01.067