Decreased expression levels of cell cycle regulators and matrix metalloproteinases in melanoma from RET-transgenic mice by single irradiation of non-equilibrium atmospheric pressure plasmas.

Since effective therapies for melanoma with BRAF(V600E) mutation are being developed, interest has been shown in the development of therapies for melanoma without BRAF(V600E) mutation. Recently, interest has also been shown in medical application of non-nequilibrium atmospheric pressure plasmas (NEAPPs). We previously suggested that repeated NEAPP irradiation to spontaneously developed benign melanocytic tumors in RFP-RET-transgenic mice (RET-mice) not only suppresses tumor growth but also prevents malignant transformation. In this study, we first confirmed that transcript expression levels of tumor growth regulators (CyclinD1, D2, E1, E2, G2 and PCNA but not CyclinG1) and tumor invasion regulators [Matrix metalloproteinase (MMP)-2, -9 and -14 and melanoma cell adhesion molecule (MCAM)] in melanomas were significantly higher than those in benign melanocytic tumors in RET-mice. We then showed that transcript expression levels of CyclinE1, G1 and G2 and MMP-2 and -9 in melanomas from RET-mice were significantly decreased by single NEAPP irradiation, whereas transcript expression levels of CyclinD1, D2, E2, PCNA, MCAM and MMP-14 were comparable in untreated and NEAPP-treated melanomas. Since no Braf(V600E) mutation melanomas have been found in RET-mice, our results suggest that single NEAPP irradiation is a potential therapeutic tool for melanoma without BRAF(V600E) mutation through modulation of the expression levels of tumor growth and invasion regulators.