Iida Machiko, Omata Yasuhiro, Nakano Chihiro, Yajima Ichiro, Tsuzuki Toyonori, Ishikawa Kenji, Hori Masaru, Kato Masashi
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan ; Department of Biomedical Sciences, Unit of Environmental Health Sciences, College of Life and Health Sciences, Chubu University Kasugai, Aichi 487-8501, Japan.
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9326-31. eCollection 2015.
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.
由于针对BRAF（V600E）突变黑色素瘤的有效疗法正在研发中，人们对BRAF（V600E）突变阴性黑色素瘤的治疗方法的研发也产生了兴趣。最近，非平衡大气压等离子体（NEAPPs）在医学应用方面也引起了关注。我们之前提出，对RFP-RET转基因小鼠（RET小鼠）自发形成的良性黑素细胞肿瘤反复进行NEAPP照射，不仅可以抑制肿瘤生长，还能预防恶性转化。在本研究中，我们首先证实，黑色素瘤中肿瘤生长调节因子（细胞周期蛋白D1、D2、E1、E2、G2和增殖细胞核抗原，但不包括细胞周期蛋白G1）和肿瘤侵袭调节因子[基质金属蛋白酶（MMP）-2、-9和-14以及黑色素瘤细胞粘附分子（MCAM）]的转录表达水平显著高于RET小鼠的良性黑素细胞肿瘤。然后我们发现，单次NEAPP照射可使RET小鼠黑色素瘤中细胞周期蛋白E1、G1和G2以及MMP-2和-9的转录表达水平显著降低，而在未处理和NEAPP处理的黑色素瘤中，细胞周期蛋白D1、D2、E2、PCNA、MCAM和MMP-14的转录表达水平相当。由于在RET小鼠中未发现Braf（V600E）突变黑色素瘤，我们的结果表明，单次NEAPP照射可能是一种通过调节肿瘤生长和侵袭调节因子的表达水平来治疗BRAF（V600E）突变阴性黑色素瘤的潜在治疗工具。
