β-eudesmol inhibits cell growth and enhances cell chemosensitivity of NPC through targeting FGF1/FGFR signaling

Abstract

Background

Chemoresistance is one of the main challenges for advanced NPC treatment. We previously proved LHX2 transcriptionally regulates FGF1 and promotes cancer progression through activating FGF1/FGFR axis,which prompted us to explore the potential inhibitors for FGFR to improve the therapy response.

Methods

RT-qPCR, immunohistochemistry, western blot assay and immunofluorescence were applied to verify the gene expression levels. Xenograft model as well as lung metastasis model was performed for in vitro assays. Flow cytometry and Tunel staining were used to determine the apoptosis of NPC cells.The interaction between β-eudesmol and FGFR1/2 was analyzed by Autodock software.

Results

 β-eudesmol inhibited the growth and metastasis of NPC in vivo and in vitro. In addition, β-eudesmol treatment promoted NPC apoptosis and sensitized NPC to cisplatin. β-eudesmol putatively bound to FGFR and blocked the Akt signaling, STAT3 signaling and ERK signaling, which in turn restrained ABCC1 transcription.

Conclusion

 β-eudesmol suppressed cell growth, metastasis and chemoresistance in NPC through targeting FGF1/FGFR signaling, thereby blocking the Akt signaling, STAT3 signaling and ERK signaling, as well as down-regulating ABCC1 expression. Our findings provided a novel potential drug for NPC treatment.