Open Access
ARTICLE
Combinatorial Effects of Plasma-Treated Solution and Plasma-Treated Hydrogel with Cisplatin in Vulvar Cancer Cells
Estelle C. I. D. Schad1,#, Janet P. Raja Xavier1,#, Hortense Decool1, Marcel Arnholdt1, Franziska Keßler1, Jan Schöttke1, Sara Y. Brucker1, Ernst Oberlechner1, Johanna Laupp1, Martin Weiss1,2,*
1 Department of Women’s Health Tübingen, University of Tübingen, Tübingen, Germany
2 Natural and Medical Sciences Institute (NMI), University of Tübingen, Reutlingen, Germany
* Corresponding Author: Martin Weiss. Email: 
# These authors contributed equally to this work
(This article belongs to the Special Issue: Advances in Cancer Therapeutics)
Oncology Research https://doi.org/10.32604/or.2026.081755
Received 08 March 2026; Accepted 18 May 2026; Published online 15 June 2026
Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
Keywords
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
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