Abstract
Oral squamous cell carcinomas (OSCCs) are one of the most prevalent malignancies, with a low five-year survival rate, thus warranting more effective drugs or therapy to improve treatment outcomes. Melatonin has been demonstrated to exhibit oncostatic effects. In this study, we explored the anti-cancer effects of melatonin on OSCCs and the underlying mechanisms. A human tongue squamous cell carcinoma cell line (SCC-15) was treated with 2 mM melatonin, followed by transwell migration and invasion assays. Relative expression levels of Fibroblast Growth Factor 19 (FGF19) was identified by Cytokine Array and further verified by qPCR and Western blot. Overexpression and downregulation of FGF19 were obtained by adding exogenous hFGF19 and FGF19 shRNA lentivirus, respectively. Invasion and migration abilities of SCC-15 cells were suppressed by melatonin, in parallel with the decreased FGF19/FGFR4 expression level. Exogenous hFGF19 eliminated the inhibitory effects of melatonin on SCC-15 cells invasion and migration, while FGF19 knocking-down showed similar inhibitory activities with melatonin. This study proves that melatonin suppresses SCC-15 cells invasion and migration through blocking the FGF19/FGFR4 pathway, which enriches our knowledge on the anticancer effects of melatonin. Blocking the FGF19/FGFR4 pathway by melatonin could be a promising alternative for OSCCs prevention and management, which would facilitate further development of novel strategies to combat OSCCs.
Highlights
Cancer is one of the leading causes of death
It was found that compared to the control group, SCC-15 cells treated with melatonin had significantly less cells invading the membrane, indicating that 2 mM melatonin significantly inhibited the migration and invasion of SCC-15 cells (Figure 1B)
We demonstrated that melatonin suppressed oral cancer cells migration and invasion, which implied that melatonin might be a potential adjuvant therapeutic for oral cancer
Summary
Cancer is one of the leading causes of death. There were over 18 million new cases and 9 million cancer-related deaths in 2018. Oral cancer was the 11th most common cancer [1]. It has high morbidity and mortality and affects nearly 600,000 people worldwide each year [2], among which 90% are oral squamous cell carcinomas (OSCCs) [3]. Surgery and adjuvant chemo-/radio-therapy have been the most widely used treatments for OSCCs. Despite the advances in technology for these treatment modalities in the past decade, the five-year survival rate of oral cancers remains low due to their rapid growth, local invasiveness, and distant metastasis [4]. Exploring the underlying mechanisms of oral cancer metastasis and developing a potential therapeutic agent for oral cancer are imperative
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