Plasma Physics and Nuclear Fusion Research School, Nuclear Science and Technology Research Institute (NSTRI), P.O. Box: 14399-53991, Tehran, Iran.
Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sci Rep. 2024 Feb 13;14(1):3578. doi: 10.1038/s41598-024-54070-4.
Recent research has highlighted the promising potential of cold atmospheric plasma (CAP) in cancer therapy. However, variations in study outcomes are attributed to differences in CAP devices and plasma parameters, which lead to diverse compositions of plasma products, including electrons, charged particles, reactive species, UV light, and heat. This study aimed to evaluate and compare the optimal exposure time, duration, and direction-dependent cellular effects of two CAPs, based on argon and helium gases, on glioblastoma U-87 MG cancer cells and an animal model of GBM. Two plasma jets were used as low-temperature plasma sources in which helium or argon gas was ionized by high voltage (4.5 kV) and frequency (20 kHz). In vitro assessments on human GBM and normal astrocyte cell lines, using MTT assays, flow cytometry analysis, wound healing assays, and immunocytochemistry for Caspase3 and P53 proteins, demonstrated that all studied plasma jets, especially indirect argon CAP, selectively induced apoptosis, hindered tumor cell growth, and inhibited migration. These effects occurred concurrently with increased intracellular levels of reactive oxygen species and decreased total antioxidant capacity in the cells. In vivo results further supported these findings, indicating that single indirect argon and direct helium CAP therapy, equal to high dose Temozolomide treatment, induced tumor cell death in a rat model of GBM. This was concurrent with a reduction in tumor size observed through PET-CT scan imaging and a significant increase in the survival rate. Additionally, there was a decrease in GFAP protein levels, a significant GBM tumor marker, and an increase in P53 protein expression based on immunohistochemical analyses. Furthermore, Ledge beam test analysis revealed general motor function improvement after indirect argon CAP therapy, similar to Temozolomide treatment. Taken together, these results suggest that CAP therapy, using indirect argon and direct helium jets, holds great promise for clinical applications in GBM treatment.
最近的研究强调了冷等离子体（CAP）在癌症治疗中的有前途的潜力。然而，研究结果的差异归因于 CAP 设备和等离子体参数的差异，这导致了等离子体产物的组成不同，包括电子、带电粒子、活性物质、紫外线和热量。本研究旨在评估和比较两种基于氩气和氦气的 CAP 的最佳暴露时间、持续时间和方向依赖性细胞效应，分别为 glioblastoma U-87 MG 癌细胞和 GBM 动物模型。两种等离子体射流被用作低温等离子体源，其中氦气或氩气通过高压（4.5 kV）和高频（20 kHz）被电离。在体外使用 MTT 测定法、流式细胞术分析、划痕愈合测定法和 Caspase3 和 P53 蛋白的免疫细胞化学评估对人 GBM 和正常星形胶质细胞系进行评估，结果表明，所有研究的等离子体射流，特别是间接氩气 CAP，选择性地诱导细胞凋亡，阻碍肿瘤细胞生长并抑制迁移。这些作用伴随着细胞内活性氧水平的增加和总抗氧化能力的降低。体内结果进一步支持了这些发现，表明单次间接氩气和直接氦气 CAP 治疗，与高剂量替莫唑胺治疗一样，在 GBM 大鼠模型中诱导肿瘤细胞死亡。这伴随着 PET-CT 扫描成像观察到的肿瘤体积减小和生存率的显著提高。此外，基于免疫组织化学分析，GFAP 蛋白水平（一种重要的 GBM 肿瘤标志物）降低，P53 蛋白表达增加。此外，间接氩气 CAP 治疗后 Ledge beam 测试分析显示总体运动功能改善，类似于替莫唑胺治疗。总之，这些结果表明，间接氩气和直接氦气射流的 CAP 治疗在 GBM 治疗的临床应用中具有广阔的前景。
