Bekeschus Sander, Rödder Katrin, Fregin Bob, Otto Oliver, Lippert Maxi, Weltmann Klaus-Dieter, Wende Kristian, Schmidt Anke, Gandhirajan Rajesh Kumar
ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.
ZIK HIKE, Fleischmannstr. 42-44, 17489 Greifswald, Germany.
Oxid Med Cell Longev. 2017;2017:4396467. doi: 10.1155/2017/4396467. Epub 2017 Jun 27.
Metastatic melanoma is an aggressive and deadly disease. Therapeutic advance has been achieved by antitumor chemo- and radiotherapy. These modalities involve the generation of reactive oxygen and nitrogen species, affecting cellular viability, migration, and immunogenicity. Such species are also created by cold physical plasma, an ionized gas capable of redox modulating cells and tissues without thermal damage. Cold plasma has been suggested for anticancer therapy. Here, melanoma cell toxicity, motility, and immunogenicity of murine metastatic melanoma cells were investigated following plasma exposure in vitro. Cells were oxidized by plasma, leading to decreased metabolic activity and cell death. Moreover, plasma decelerated melanoma cell growth, viability, and cell cycling. This was accompanied by increased cellular stiffness and upregulation of zonula occludens 1 protein in the cell membrane. Importantly, expression levels of immunogenic cell surface molecules such as major histocompatibility complex I, calreticulin, and melanocortin receptor 1 were significantly increased in response to plasma. Finally, plasma treatment significantly decreased the release of vascular endothelial growth factor, a molecule with importance in angiogenesis. Altogether, these results suggest beneficial toxicity of cold plasma in murine melanomas with a concomitant immunogenicity of potential interest in oncology.
转移性黑色素瘤是一种侵袭性致命疾病。抗肿瘤化疗和放疗已取得治疗进展。这些治疗方式会产生活性氧和氮物质,影响细胞活力、迁移和免疫原性。冷物理等离子体也能产生这些物质,它是一种能在不造成热损伤的情况下对细胞和组织进行氧化还原调节的电离气体。冷等离子体已被提议用于抗癌治疗。在此,研究了体外等离子体处理后小鼠转移性黑色素瘤细胞的毒性、运动性和免疫原性。细胞被等离子体氧化,导致代谢活性降低和细胞死亡。此外,等离子体减缓了黑色素瘤细胞的生长、活力和细胞周期进程。这伴随着细胞硬度增加以及细胞膜中紧密连接蛋白1的上调。重要的是,免疫原性细胞表面分子如主要组织相容性复合体I、钙网蛋白和黑皮质素受体1的表达水平因等离子体处理而显著增加。最后,等离子体处理显著降低了血管内皮生长因子的释放,该分子在血管生成中具有重要作用。总之,这些结果表明冷等离子体对小鼠黑色素瘤具有有益的毒性,并具有肿瘤学方面潜在的免疫原性。