Stoof Jojanneke, Kalmoua Zakaria, Sobota Ana, Brakenhoff Ruud H, Stigter Marijke, Pham Thang V, Piersma Sander R, Henneman Alex, Lagerweij Tonny, de Goeij-de Haas Richard, van Moorselaar R Jeroen A, Jimenez Connie R, Bijnsdorp Irene V
Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, de Boelelaan 1117, 1018 HV, Amsterdam, The Netherlands.
Amsterdam UMC, Location VUmc, Urology, Amsterdam, The Netherlands.
Sci Rep. 2025 Jan 17;15(1):2334. doi: 10.1038/s41598-025-85568-0.
Bladder cancer often recurs, necessitating innovative treatments to reduce recurrence. We investigated non-thermal plasma's potential as a novel anti-cancer therapy, focusing on plasma-activated solution (PAS), created by exposing saline to non-thermal plasma. Our study aims to elucidate the biological effects of PAS on bladder cancer cell lines in vitro, as well as the combination with mitomycin C (MMC), using clinically relevant settings. PAS treatment exerts a potent cytotoxic effect through the production of intracellular reactive oxygen species, resulting in DNA damage and subsequent induction of G1 cell cycle arrest/senescence. This is induced via upregulation of cell cycle checkpoint signalling and DNA damage repair pathways using LC-M/MS-based phospho-proteomics. Importantly, combining PAS with MMC reveals a synergistic effect (Combination Index of 0.59-0.67), suggesting the potential of utilizing PAS in combination therapies. Our findings demonstrate PAS's mode of action and suggest its potential as a promising treatment for bladder cancer, warranting further clinical studies.
膀胱癌常复发，因此需要创新疗法来降低复发率。我们研究了非热等离子体作为一种新型抗癌疗法的潜力，重点关注通过将盐水暴露于非热等离子体而产生的等离子体激活溶液（PAS）。我们的研究旨在阐明PAS在体外对膀胱癌细胞系的生物学效应，以及在临床相关环境中与丝裂霉素C（MMC）联合使用的情况。PAS处理通过产生细胞内活性氧发挥强大的细胞毒性作用，导致DNA损伤并随后诱导G1期细胞周期停滞/衰老。这是通过基于液相色谱-质谱联用（LC-M/MS）的磷酸化蛋白质组学上调细胞周期检查点信号和DNA损伤修复途径来诱导的。重要的是，将PAS与MMC联合使用显示出协同效应（联合指数为0.59-0.67），这表明在联合疗法中使用PAS的潜力。我们的研究结果证明了PAS的作用模式，并表明其作为膀胱癌有前景的治疗方法的潜力，值得进一步的临床研究。
