Document Type

Article

Publication Date

2026

Publication Title

International Journal of Molecular Sciences

Volume

27

Issue

13

Pages

5933

DOI

10.3390/ijms27135933

Abstract

Pancreatic cancer remains a highly lethal malignancy, with standard therapies offering limited benefits in advanced stages; thus, novel strategies that exploit specific cancer cell vulnerabilities are urgently needed. Building on our previous findings that nanosecond pulsed electric fields (nsPEF) combined with cold atmospheric plasma (CAP) produce enhanced cytotoxicity, this study investigates the molecular mechanisms underlying this synergy. Pan02 pancreatic cancer cells were subjected to nsPEF, CAP, or a combination of both. We assessed cell viability, reactive oxygen species (ROS) production, and mitochondrial integrity using metabolic assays, flow cytometry, and fluorescence microscopy. Apoptotic markers were evaluated via Western blotting and caspase activity assays. Combined nsPEF-CAP treatment significantly outperformed either modality alone in inducing cell death. Mechanistically, dual treatment triggered a surge in intracellular ROS, particularly mitochondrial superoxide, indicating severe oxidative stress. Distinct mitochondrial responses were observed: nsPEF reduced mitochondrial membrane potential, whereas CAP alone caused a slight elevation. Notably, while CAP induced apoptosis (evidenced by increased cleaved caspase-3 and caspase-3/7 activity), lethal nsPEF (100 pulses) caused cell death without triggering apoptotic signaling. However, mild nsPEF (20 pulses) significantly potentiated CAP-induced apoptosis. These findings suggest that nsPEF sensitizes cells to CAP treatment by amplifying oxidative stress and mitochondrial dysfunction. This synergistic combination represents a promising therapeutic approach for managing pancreatic cancer cells resistant to conventional therapies.

Rights

© 2026 by the authors.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Data Availability

Article states: "The original contributions presented in this study are included in the article, further inquiries can be directed to the corresponding author."

Original Publication Citation

Minhas, Z., Oshin, E. A., Yang, L., Jiang, C., & Guo, S. (2026). Synergistic sensitization of pancreatic cancer cells by nanosecond pulsed electric fields and cold atmospheric plasma via amplifying ROS and apoptotic signaling. International Journal of Molecular Sciences, 27(13), Article 5933. https://doi.org/10.3390/ijms27135933

ORCID

0009-0009-8605-6390 (Minhas), 0000-0002-2932-9470 (Oshin), 0000-0001-9711-5768 (Yang), 0000-0002-7280-7888 (Guo)

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