Medical gas plasma augments bladder cancer cell toxicity in preclinical models and patient-derived tumor tissues

医用气体等离子体增强临床前模型和患者来源的肿瘤组织中的膀胱癌细胞毒性

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作者:Nadine Gelbrich, Lea Miebach, Julia Berner, Eric Freund, Fariba Saadati, Anke Schmidt, Matthias Stope, Uwe Zimmermann, Martin Burchardt, Sander Bekeschus

Conclusion

Gas plasma treatment induced cytotoxicity in patient-derived cancer tissue and slowed tumor growth in an organoid model of urinary bladder carcinoma, along with less severe effects in non-malignant tissues. Studies on the potential clinical benefits of this local and safe ROS therapy are awaited.

Methods

2D cell culture models, 3D tumor spheroids, 3D vascularized tumors grown on the chicken chorion-allantois-membrane (CAM) in ovo, and patient-derived primary cancer tissue gas plasma-treated ex vivo were used.

Results

Gas plasma treatment led to oxidation, growth retardation, motility inhibition, and cell death in 2D and 3D tumor models. A marked decline in tumor growth was also observed in the tumors grown in ovo. In addition, results of gas plasma treatment on primary urothelial carcinoma tissues ex vivo highlighted the selective tumor-toxic effects as non-malignant tissue exposed to gas plasma was less affected. Whole-transcriptome gene expression analysis revealed downregulation of tumor-promoting fibroblast growth factor receptor 3 (FGFR3) accompanied by upregulation of apoptosis-inducing factor 2 (AIFm2), which plays a central role in caspase-independent cell death signaling.

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