Abstract

The treatment of solid tumors by a cold atmospheric plasma (CAP) jet is an innovative approach that has been actively developed only in the last decade. As a result, studies aimed at identifying the conditions for selective effect on tumor cells, including as parts of 3D models that mimic malignant neoplasms are pertinent. It is known that the main cytotoxic effects of a CAP are caused by reactive oxygen and nitrogen species in the plasma jet. Their availability for cells in classical 2D and 3D models of cell cultivation may be different. Here, we used multicellular spheroids of MCF7–EGFR cells with overexpression of the epidermal growth-factor receptor (EGFR), cells of parental breast adenocarcinoma MCF7 cell line, and nontransformed human breast cells MCF10A. Irradiation of MCF7–EGFR spheroids induced destruction of multicellular 3D structures into individual cells and activated cell death. It has been shown that the cells of irradiated spheroids undergo phagocytosis by activated macrophages. Comparison of a direct CAP irradiation of MCF7–EGFR spheroids and indirect treatment with plasma-activated medium (PAM) revealed a higher content of reactive oxygen and nitrogen species in spheroid cells cultivated in the irradiated medium. It produced a higher cytotoxic effect than direct irradiation. It has been shown that the cytotoxic properties of PAM are better preserved when such a medium is stored at 4° than at –20°C. Thus, the death of tumor cells in spheroids was more effective with addition of the culture medium irradiated with a CAP than direct irradiation of cells.

中文翻译：

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与人类乳腺癌 3D 细胞模型相关的冷大气等离子体射流的细胞毒活性

摘要

通过冷大气等离子体 (CAP) 射流治疗实体瘤是一种创新方法，仅在过去十年才得到积极开发。因此，旨在确定对肿瘤细胞产生选择性作用的条件的研究是相关的，包括作为模拟恶性肿瘤的 3D 模型的一部分。众所周知，CAP 的主要细胞毒性作用是由等离子体射流中的活性氧和氮物种引起的。它们在细胞培养的经典 2D 和 3D 模型中对细胞的可用性可能不同。在这里，我们使用了表皮生长因子受体 (EGFR) 过表达的 MCF7–EGFR 细胞的多细胞球体、亲代乳腺癌 MCF7 细胞系和未转化的人乳腺细胞 MCF10A。MCF7-EGFR 球状体的辐照诱导多细胞 3D 结构破坏成单个细胞并激活细胞死亡。已经表明，辐照球体的细胞会被活化的巨噬细胞吞噬。比较 MCF7–EGFR 球状体的直接 CAP 照射和等离子体活化培养基 (PAM) 的间接处理表明，在受辐照的培养基中培养的球状细胞中活性氧和氮物质含量更高。它产生比直接照射更高的细胞毒性作用。已经表明，当这种培养基在 4°C 下储存时，PAM 的细胞毒性特性比 –20°C 下保存得更好。因此，与直接照射细胞相比，添加用 CAP 照射的培养基可更有效地杀死球状体中的肿瘤细胞。