Integrin αvβ3-Akt signalling plays a role in radioresistance of melanoma

Melanoma is a deadly type of skin cancer that is particularly difficult to treat owing to its resistance to radiation therapy. Here, we attempted to determine the key proteins responsible for melanoma radioresistance, with the aim of improving disease response to radiation therapy. Two melanoma cell lines, SK-Mel5 and SK-Mel28, with different radiosensitivities were analysed via RNA-Seq (Quant-Seq) and target proteins with higher abundance in the more radioresistant cell line, SK-Mel28, identified. Among these proteins, integrin αvβ3, a well-known molecule in cell adhesion, was selected for analysis. Treatment of SK-Mel28 cells with cilengitide, an integrin αvβ3 inhibitor, as well as γ-irradiation resulted in more significant cell death than γ-irradiation alone. In addition, Akt, a downstream signal transducer of integrin αvβ3, showed high basic activation in SK-Mel28 and was significantly decreased upon co-treatment with cilengitide and γ-irradiation. MK-2206, an Akt inhibitor, exerted similar effects on the SK-Mel28 cell line following γ-irradiation. Our results collectively demonstrate that the integrin αvβ3-Akt signalling pathway contributes to radioresistance in SK-Mel28 cells, which may be manipulated to improve therapeutic options for melanoma.