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一种创新性的骨肉瘤和尤文肉瘤治疗选择：利用物理气体等离子体消除成骨性和尤文氏肉瘤细胞。

An Innovative Therapeutic Option for the Treatment of Skeletal Sarcomas: Elimination of Osteo- and Ewing's Sarcoma Cells Using Physical Gas Plasma.

机构信息

Department of Trauma, Reconstructive Surgery and Rehabilitation Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, Germany.

ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Straße 2, 17489 Greifswald, Germany.

出版信息

Int J Mol Sci. 2020 Jun 23;21(12):4460. doi: 10.3390/ijms21124460.

DOI:10.3390/ijms21124460
PMID:32585948
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7352911/
Abstract

Osteosarcoma and Ewing's sarcoma are the most common malignant bone tumors. Conventional therapies such as polychemotherapy, local surgery, and radiotherapy improve the clinical outcome for patients. However, they are accompanied by acute and chronic side effects that affect the quality of life of patients, motivating novel research lines on therapeutic options for the treatment of sarcomas. Previous experimental work with physical plasma operated at body temperature (cold atmospheric plasma, CAP) demonstrated anti-oncogenic effects on different cancer cell types. This study investigated the anti-cancer effect of CAP on two bone sarcoma entities, osteosarcoma and Ewing's sarcoma, which were represented by four cell lines (U2-OS, MNNG/HOS, A673, and RD-ES). A time-dependent anti-proliferative effect of CAP on all cell lines was observed. CAP-induced alterations in cell membrane functionality were detected by performing a fluorescein diacetate (FDA) release assay and an ATP release assay. Additionally, modifications of the cell membrane and modifications in the actin cytoskeleton composition were examined using fluorescence microscopy monitoring dextran-uptake assay and G-/F-actin distribution. Furthermore, the CAP-induced induction of apoptosis was determined by TUNEL and active caspases assays. The observations suggest that a single CAP treatment of bone sarcoma cells may have significant anti-oncogenic effects and thus may be a promising extension to existing applications.

摘要

骨肉瘤和尤文肉瘤是最常见的恶性骨肿瘤。多化疗、局部手术和放疗等传统疗法改善了患者的临床预后。然而，它们伴随着急性和慢性副作用，影响患者的生活质量，这促使人们开展了治疗肉瘤的治疗选择的新研究。先前在体温下（冷大气压等离子体，CAP）进行的物理等离子体的实验工作已经证明了对不同癌症细胞类型的抗致癌作用。本研究调查了 CAP 对两种骨肉瘤实体，骨肉瘤和尤文肉瘤的抗癌作用，这两种肉瘤由四种细胞系（U2-OS、MNNG/HOS、A673 和 RD-ES）代表。观察到 CAP 对所有细胞系的时间依赖性抗增殖作用。通过进行荧光素二乙酸（FDA）释放测定和 ATP 释放测定，检测到 CAP 诱导的细胞膜功能改变。此外，通过荧光显微镜监测葡聚糖摄取测定和 G-/F-肌动蛋白分布，检查细胞膜的修饰和肌动蛋白细胞骨架成分的修饰。此外，通过 TUNEL 和活性半胱天冬酶测定确定 CAP 诱导的细胞凋亡。这些观察结果表明，单次 CAP 处理骨肉瘤细胞可能具有显著的抗癌作用，因此可能是现有应用的有前途的扩展。

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