Tepotinib suppresses proliferation, invasion, migration, and promotes apoptosis of melanoma cells via inhibiting MET and PI3K/AKT signaling pathways

Malignant melanoma seriously threatens public health and lowers the quality of life of the affected subjects. The present study was designed to explore the effects of tepotinib, a selective tyrosine kinase inhibitor of MET proto-oncogene, receptor tyrosine kinase (MET), on the progression of melanoma. Firstly, MTT assays were used to detect the proliferation of tepotinib-treated WM451 cells. The cell invasive and migratory activities were assessed using Transwell and wound healing assays, respectively. In addition, TUNEL staining was employed to determine cell apoptosis. Western blot analysis was utilized for the evaluation of the expression levels of apoptotic and epithelial-mesenchymal transition-related proteins, as well as of proteins involved in the PI3K/AKT signaling pathway. Subsequently, hepatocyte growth factor (HGF), a natural agonist of MET, was administered to WM451 cells to unravel the detailed mechanism of action of tepotinib in melanoma. The results indicated that the proliferation of WM451 cells was significantly decreased by tepotinib treatment. The inhibitory effects of tepotinib on the proliferation of WM451 cells occurred in a concentration-dependent manner. In addition, the migratory and invasive activities of WM451 cells were significantly suppressed following tepotinib treatment. It was also shown that tepotinib exhibited promotive effects on the induction of apoptosis of WM451 cells. Moreover, activation of MET and PI3K/AKT signaling pathways may be blocked by tepotinib treatment, whereas addition of HGF to the cells reversed the effects of tepotinib treatment on the malignant progression of WM451 cells. In conclusion, the data demonstrated that tepotinib suppressed the proliferation, invasion and migration of melanoma cells, whereas it could also induce their apoptosis. This evidence may provide a new perspective for the improvement of malignant melanoma.