Melatonin inhibits OSCCs progression through FGF19/FGFR4 Signaling Pathway.

Abstract

Objectives: Oral squamous cell carcinomas (OSCCs) are one of the most prevalent malignancies throughout the world with a low 5-year survival rate and thus warrants novel effective drugs or treatment methods. Melatonin is an endogenous hormone that has various functions on human pathology and physiology such as antioxidant activity, anti-inflammation, and immunomodulation. Recent evidence has made melatonin a promising adjunct in the management and prevention of OSCCs. This study further explored the underlying mechanisms in detail. Methods: The human tongue squamous cell carcinoma cell line (SCC-15) was treated with 2 mM melatonin. Transwell migration and invasion assays were conducted at 24h or 48h. FGF19/FGFR4 mRNA and protein expression levels were tested by qPCR and western blot. Overexpression and downregulation of FGF19 were obtained by adding exogenous hFGF19 and FGF19 shRNA lentivirus, respectively. Results: Invasion and migration abilities of SCC-15 were inhibited by melatonin, in parallel with the decreased FGF19/FGFR4 mRNA and protein expression level. Exogenous hFGF19 can eliminate the inhibitory effects of melatonin on SCC-15 invasion and migration while knocking down FGF19 by lentivirus showed similar inhibitory effects with melatonin. Conclusions: Our current work proved that melatonin inhibits SCC-15 invasion and migration by blocking FGF19/FGFR4 pathway. This result enriches our understanding on the role of melatonin in the management and prevention of OSCCs, which would facilitate further development of novel strategies to combat OSCCs.