Combinatorial Effects of Plasma-Treated Solution and Plasma-Treated Hydrogel with Cisplatin in Vulvar Cancer Cells

Sep 23, 2026

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Vulvar squamous cell carcinoma (VSCC) is an increasingly prevalent malignancy with limited options in advanced disease, where cisplatin-based chemoradiation is standard but limited by cumulative toxicity. This study compares plasma-treated solution (PTS) and plasma-treated hydrogel (PTH), used alone or sequentially with cisplatin (plasma-first vs cisplatin-first), to determine redox-driven anti-tumor efficacy. PTS rapidly increases reactive oxygen and nitrogen species (RONS), while PTH releases RONS more delayed and sustained. Plasma pretreatment boosts cisplatin effectiveness and synergy, reflected by increased caspase-3/7 activity and lowered GSH/GSSG ratios, indicating oxidative stress and apoptotic priming. Results support integrating PTS/PTH into combinatorial strategies for VSCC and related precancerous lesions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages24

Reading Time1 h 0 min

AccessFree to download

Introduction

Rationale for vulvar cancer treatment approaches

Role and limitations of cisplatin-based chemoradiation

Abstract Overview

Background: VSCC and precursor lesions

Methods: PTS/PTH and sequential cisplatin design

Results: RONS kinetics, viability, synergy, apoptosis

Conclusions: redox modulation and combinatorial potential

| [http://doi.org/10.32604/or.2026.081755](http://doi.org/10.32604/or.2026.081755) | | | --- | --- | | | | | ARTICLE
Combinatorial Effects of Plasma-Treated Solution and Plasma-Treated Hydrogel with Cisplatin in Vulvar Cancer Cells
Estelle C. I. D. Schad 1,\# , Janet P. Raja Xavier 1,\# , Hortense Decool1 , Marcel Arnholdt 1 , Franziska Keßler 1 , Jan Schöttke 1 , Sara Y. Brucker 1 , Ernst Oberlechner 1 , Johanna Laupp 1 and Martin Weiss 1,2, *
1Department of Women’s Health Tübingen, University ofTübingen, Tübingen, Germany
2Natural and Medical Sciences Institute (NMI), University ofTübingen, Reutlingen, Germany
*[Corresponding Author: Martin Weiss. Email: martin.weiss@med.uni-tuebingen.de](Corresponding Author: Martin Weiss. Email: martin.weiss@med.uni-tuebingen.de)
[\#](# These authors contributed equally to this work)[ These authors contributed equally to this work](# These authors contributed equally to this work)
Received: 08 March 2026; Accepted: 18 May 2026; Published: 13 August 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 ina 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 plasma (NIPP); cold atmospheric plasma (CAP); reactive oxygen and nitrogen species; combination therapy | | 1 Introduction Vulvar cancer is the fourth most common gynecological malignancy worldwide, accounting for approximately 4% of all cancers affecting the female genital tract [1] . Although relatively rare, its incidence is steadily increasing, with the mean age of incidence falling [1,2] . The majority of vulvar cancers are squamous cell carcinomas (VSCC), while other less common types include vulvar melanoma, basal cell carcinoma (BCC), and Paget’s disease. Many cases of VSCC arise from precancerous lesions, which are classified based Copyright © 2026 The Authors. Published by Tech Science Press. This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and re

FAQs

What was the study’s main objective regarding plasma and cisplatin in VSCC cells?

To evaluate whether plasma-treated solution (PTS) and plasma-treated hydrogel (PTH), alone or sequentially with cisplatin, improve anti-tumor efficacy in vulvar cancer cells via redox modulation.

How did PTS and PTH differ in reactive oxygen and nitrogen species (RONS) release?

PTS caused a rapid oxidative burst, whereas PTH enabled delayed and sustained RONS release.

What evidence indicated enhanced oxidative stress and apoptosis when combining plasma with cisplatin?

In plasma-cisplatin combination treatments, caspase-3/7 activity increased and GSH/GSSG ratios decreased, consistent with enhanced oxidative stress and apoptotic priming.

Sep 23, 2026

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