冷大气压等离子体治疗抑制血管生成——一种有前景的肿瘤治疗方法。
Inhibition of Angiogenesis by Treatment with Cold Atmospheric Plasma as a Promising Therapeutic Approach in Oncology.
机构信息
Department of Trauma, Reconstructive Surgery and Rehabilitation Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, Germany.
Department of Trauma and Orthopaedic Surgery, BG Klinikum Unfallkrankenhaus Berlin gGmbH, Warener Straße 7, 12683 Berlin, Germany.
出版信息
Int J Mol Sci. 2020 Sep 26;21(19):7098. doi: 10.3390/ijms21197098.
BACKGROUND
Cold atmospheric plasma (CAP) is increasingly used in the field of oncology. Many of the mechanisms of action of CAP, such as inhibiting proliferation, DNA breakage, or the destruction of cell membrane integrity, have been investigated in many different types of tumors. In this regard, data are available from both in vivo and in vitro studies. Not only the direct treatment of a tumor but also the influence on its blood supply play a decisive role in the success of the therapy and the patient's further prognosis. Whether the CAP influences this process is unknown, and the first indications in this regard are addressed in this study.
METHODS
Two different devices, kINPen and MiniJet, were used as CAP sources. Human endothelial cell line HDMEC were treated directly and indirectly with CAP, and growth kinetics were performed. To indicate apoptotic processes, caspase-3/7 assay and TUNEL assay were used. The influence of CAP on cellular metabolism was examined using the MTT and glucose assay. After CAP exposure, tube formation assay was performed to examine the capillary tube formation abilities of HDMEC and their migration was messured in separate assays. To investigate in a possible mutagenic effect of CAP treatment, a hypoxanthine-guanine-phosphoribosyl-transferase assay with non malignant cell (CCL-93) line was performed.
RESULTS
The direct CAP treatment of the HDMEC showed a robust growth-inhibiting effect, but the indirect one did not. The MMT assay showed an apparent reduction in cell metabolism in the first 24 h after CAP treatment, which appeared to normalize 48 h and 72 h after CAP application. These results were also confirmed by the glucose assay. The caspase 3/7 assay and TUNEL assay showed a significant increase in apoptotic processes in the HDMEC after CAP treatment. These results were independent of the CAP device. Both the migration and tube formation of HDMEC were significant inhibited after CAP-treatment. No malignant effects could be demonstrated by the CAP treatment on a non-malignant cell line.
背景
冷等离体等离子体（CAP）在肿瘤学领域的应用日益广泛。CAP 的许多作用机制，如抑制增殖、DNA 断裂或破坏细胞膜完整性，已在许多不同类型的肿瘤中得到研究。在这方面，既有体内研究数据，也有体外研究数据。不仅肿瘤的直接治疗，其血液供应的影响对治疗的成功和患者的进一步预后也起着决定性的作用。CAP 是否会影响这一过程尚不清楚，本研究首次对此进行了探讨。
方法
采用 kINPen 和 MiniJet 两种不同的设备作为 CAP 源。直接和间接用 CAP 处理人内皮细胞系 HDMEC，并进行生长动力学研究。为了指示细胞凋亡过程，使用 caspase-3/7 测定法和 TUNEL 测定法。使用 MTT 和葡萄糖测定法检测 CAP 对细胞代谢的影响。CAP 暴露后，进行管形成测定以检查 HDMEC 的毛细血管管形成能力，并在单独的测定中测量其迁移。为了研究 CAP 处理的潜在诱变效应，用非恶性细胞（CCL-93 系）进行次黄嘌呤鸟嘌呤磷酸核糖转移酶测定。
结果
HDMEC 的直接 CAP 处理显示出强大的生长抑制作用，但间接处理则没有。MTT 测定显示，CAP 处理后 24 小时内细胞代谢明显减少，48 小时和 72 小时后似乎恢复正常。葡萄糖测定也证实了这一结果。CAP 处理后，HDMEC 中的细胞凋亡过程明显增加，caspase 3/7 测定法和 TUNEL 测定法均显示出这一结果。这些结果与 CAP 装置无关。CAP 处理后，HDMEC 的迁移和管形成均受到显著抑制。CAP 处理对非恶性细胞系没有显示出恶性影响。
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