- Bleomycin-based ECT via custom bipolar electrode produced pronounced tumour disruption and significant reductions in tumour area and perimeter in ovo, less significant ex vivo.
- Treatment decreased melanoma-associated marker expression, including Sox10, across multiple in ovo and selected ex vivo conditions, indicating reduced tumour differentiation.
- ECT triggered multiple cell death pathways in ovo, with significant apoptosis, pyroptosis, necrosis and necroptosis changes, and responses varied by model and EP settings.
Front Cell Dev Biol. 2026 Sep 8;14:1860536. doi: 10.3389/fcell.2026.1860536. eCollection 2026.
ABSTRACT
INTRODUCTION: Uveal melanoma (UM) is a rare tumor entity and the predominant primary intraocular malignancy in adulthood. Despite high local tumor control rates, metastatic disease remains frequent and systemic therapeutic options are limited. Electrochemotherapy (ECT) with bleomycin enhances intracellular drug uptake through electroporation (EP), thereby increasing targeted antitumor activity. This study investigated the effects of bleomycin-based ECT delivered using a custom bipolar electrode in UM patient-derived xenografts (PDX).
METHODS: UM PDX were analyzed in both in ovo and ex vivo experimental settings. Tumor grafts were treated with EP alone at voltage settings of 750 V or 1000 V, or with ECT combined with bleomycin at concentrations of 1 μg/mL or 2.5 μg/mL. Histological evaluation and immunofluorescence analyses were performed to assess tumor morphology, melanoma-associated marker expression, vascularization, proliferative activity and treatment-induced cell death pathways.
RESULTS: ECT caused pronounced tumor disruption and decreased tumor size parameters compared with untreated controls, with statistically significant reductions in tumor area following EP at 750 V alone or combined with 2.5 μg/mL bleomycin and in tumor perimeter across all groups treated with EP at 750 V in ovo, while changes in the ex vivo model were not statistically significant. Expression of melanoma-associated markers, including a melanoma marker cocktail and Sox10, decreased following treatment, with significant differences observed in multiple in ovo and selected ex vivo conditions. Analysis of cell death markers indicated involvement of multiple cell death mechanisms, with statistically significant treatment-associated changes in markers of apoptosis, pyroptosis, necrosis and necroptosis detected in ovo, whereas gasdermin D expression did not reach statistical significance ex vivo. Treatment responses differed between experimental models and EP conditions, suggesting model-dependent cellular responses.
DISCUSSION: Bleomycin-based ECT using a custom bipolar electrode induces substantial tumor damage in UM PDX in ovo and ex vivo. These findings support the potential application of bipolar electrode-based ECT for intraocular tumor treatment and provide a basis for further optimization of electrode design and translational investigation.
PMID:42787544 | PMC:PMC13602299 | DOI:10.3389/fcell.2026.1860536
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