Gkantaras Antonios, Kotzamanidis Charalampos, Kyriakidis Konstantinos, Farmaki Evangelia, Makedou Kali, Tzimagiorgis Georgios, Bekeschus Sander, Malousi Andigoni
Laboratory of Biological Chemistry, Medical School, Aristotle University, 54124 Thessaloniki, Greece.
Pediatric Immunology and Rheumatology Referral Center, 1st Department of Pediatrics, Aristotle University, 54124 Thessaloniki, Greece.
Cancers (Basel). 2024 Jun 10;16(12):2186. doi: 10.3390/cancers16122186.
The therapeutic potential of cold physical gas plasma operated at atmospheric pressure in oncology has been thoroughly demonstrated in numerous preclinical studies. The cytotoxic effect on malignant cells has been attributed mainly to biologically active plasma-generated compounds, namely, reactive oxygen and nitrogen species. The intracellular accumulation of reactive oxygen and nitrogen species interferes strongly with the antioxidant defense system of malignant cells, activating multiple signaling cascades and inevitably leading to oxidative stress-induced cell death. This study aims to determine whether plasma-induced cancer cell death operates through a universal molecular mechanism that is independent of the cancer cell type. Using whole transcriptome data, we sought to investigate the activation mechanism of plasma-treated samples in patient-derived prostate cell cultures, melanoma, breast, lymphoma, and lung cancer cells. The results from the standardized single-cohort gene expression analysis and parallel multi-cohort meta-analysis strongly indicate that plasma treatment globally induces cancer cell death through immune-mediated mechanisms, such as interleukin signaling, Toll-like receptor cascades, and MyD88 activation leading to pro-inflammatory cytokine release and tumor antigen presentation.
常压下冷物理气体等离子体在肿瘤学中的治疗潜力已在众多临床前研究中得到充分证明。对恶性细胞的细胞毒性作用主要归因于生物活性等离子体产生的化合物，即活性氧和氮物种。活性氧和氮物种在细胞内的积累强烈干扰恶性细胞的抗氧化防御系统，激活多个信号级联反应，并不可避免地导致氧化应激诱导的细胞死亡。本研究旨在确定等离子体诱导的癌细胞死亡是否通过一种独立于癌细胞类型的通用分子机制发生。利用全转录组数据，我们试图研究等离子体处理的样本在患者来源的前列腺细胞培养物、黑色素瘤、乳腺癌、淋巴瘤和肺癌细胞中的激活机制。标准化单队列基因表达分析和平行多队列荟萃分析的结果有力地表明，等离子体处理通过免疫介导的机制全局诱导癌细胞死亡，如白细胞介素信号传导、Toll样受体级联反应和MyD88激活，导致促炎细胞因子释放和肿瘤抗原呈递。
