TY  - EJOU
AU  - Schad, Estelle C. I. D. 
AU  - Xavier, Janet P. Raja 
AU  - Decool, Hortense 
AU  - Arnholdt, Marcel 
AU  - Keßler, Franziska 
AU  - Schöttke, Jan 
AU  - Brucker, Sara Y. 
AU  - Oberlechner, Ernst 
AU  - Laupp, Johanna 
AU  - Weiss, Martin 

TI  - Combinatorial Effects of Plasma-Treated Solution and Plasma-Treated Hydrogel with Cisplatin in Vulvar Cancer Cells
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - <b>Background:</b> Vulvar squamous cell carcinoma (VSCC) is a rare, but increasingly prevalent malignancy with limited therapeutic options in the advanced disease state. Cisplatin-based chemoradiation remains the standard of care but is constrained by cumulative toxicity. Precancerous lesions, including high-grade squamous intraepithelial lesions (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN), similarly require effective yet tolerable treatments. Low-thermal Argon plasma devitalization (ltAPD), a source of reactive oxygen and nitrogen species (RONS), has emerged as a promising approach for redox-based tumor modulation. This study aimed to evaluate the anti-tumor efficacy of two plasma modalities, plasma-treated solution (PTS) and plasma-treated hydrogel (PTH) in combination with cisplatin in VSCC cells. <b>Methods:</b> PTS and PTH were applied as monotherapies and in sequential combination with cisplatin (plasma-first vs. cisplatin-first). RONS kinetics, cell viability, and treatment interactions were assessed following plasma monotherapy and sequential combination with cisplatin. Apoptosis and redox balance were evaluated by caspase-3/7 activity and GSH/GSSG ratios, respectively. <b>Results:</b> PTS induced a rapid oxidative burst, whereas PTH enabled delayed and sustained RONS release. Both modalities reduced cell viability in a time-dependent manner, with rapid cytotoxic effects observed for PTS. Plasma pre-treatment enhanced cisplatin efficacy, with higher synergy scores in the plasma-first sequence. Increased caspase-3/7 activity and decreased GSH/GSSG ratios, observed in the combination treatment of plasma and cisplatin, indicated enhanced oxidative stress and apoptotic priming. <b>Conclusions:</b> PTS and PTH exhibit intrinsic anti-tumor activity and sensitize VSCC cells to cisplatin through redox modulation. These findings support the integration of plasma-based strategies into combinatorial therapeutic approaches for VSCC and its precancerous lesions.
KW  - Vulvar squamous cell carcinoma; low-thermal argon plasma devitalization (ltAPD); non-invasive physical plasmaa (NIPP); cold atmospheric plasma (CAP); reactive oxygen and nitrogen species; combination therapy

DO  - 10.32604/or.2026.081755