Nintedanib induces apoptosis in human pterygium cells through the FGFR2-ERK signalling pathway.

Aim: To investigate whether nintedanib can inhibit pterygium cells through the fibroblast growth factor receptor 2 (FGFR2)/extracellular-signal-regulated kinase (ERK) pathway.
Methods: Human primary pterygium cells were cultured in vitro . After treatment with nintedanib, the cell morphology was observed under microscopy, the morphological changes of the nucleus were observed after DAPI staining, apoptosis was analyzed by Annexin-V FITC/PI double staining, and the changes of apoptosis-associated proteins were detected by Western blot. The binding ability of nintedanib to FGFR2 was predicted by molecular docking. Finally, by silencing FGFR2, we explored whether nintedanib inhibited FGFR2/ERK pathway.
Results: The results showed that nintedanib inhibited the growth of pterygium cells and caused nuclear pyknosis. The results of Annexin-VFITC/PI double staining showed that nintedanib was able to induce early and late apoptosis of pterygium cells, significantly increasing the expression of apoptosis-associated proteins Bax and cleaved-Caspase3 ( P <0.05), and reducing the expression of Bcl-2 ( P <0.05). In addition, nintedanib significantly inhibited ERK1/2 phosphorylation through FGFR2 ( P <0.05). After silencing the expression of FGFR2, there was no significant difference in the inhibition of ERK1/2 phosphorylation by nintedanib ( P >0.05).
Conclusion: Nintedanib induces apoptosis of pterygium cells by inhibiting FGFR2/ERK pathway.
(International Journal of Ophthalmology Press.)