Abstract

In recent years, the emerging technology of cold atmospheric pressure plasma (CAP) has grown rapidly along with the many medical applications of cold plasma (e.g., cancer, skin disease, tissue repair, etc.). Plasma-activated liquids (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as cancer treatments, and due to their advantages, many researchers prefer plasma-activated liquids as an alternative to CAP in the treatment of cancer. In this study, we showed that plasma-activated-saline (PAS) treatment significantly inhibited tumor growth, as compared with saline, in melanoma, and a low-pH environment had little effect on tumor growth in vivo. In addition, based on an ultra-high-performance liquid tandem chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) analysis of tumor cell metabolism, the glycerophospholipid metabolic pathway was the most susceptible metabolic pathway to PAS treatment in melanoma in vitro and in vivo. Furthermore, PAS also inhibited cell proliferation in vivo in oral tongue squamous-cell cancer and non-small-cell lung cancer. There were few toxic side effects in the three animal models, and the treatment was deemed safe to use. In the future, plasma-activated liquids may serve as a potential therapeutic approach in the treatment of cancer.

Highlights

  • Published: 23 February 2022Melanoma is one of the most common malignant tumors in clinical practice

  • Immunotherapy based on the programmed death 1 (PD-1) pathway has been effective for advanced melanoma, the overall objective response rate has been around 33% in recent clinical studies [2], suggesting that a majority of melanoma patients may need alternative treatment strategies

  • We found that plasma-activated saline (PAS) treatment significantly suppressed tumor growth, as compared to saline treatment on melanomas (A375 cell line) in vivo

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Summary

Introduction

Melanoma is one of the most common malignant tumors in clinical practice. With the emergence of molecular-targeted therapy and immunotherapy, the treatment of metastatic melanoma has undergone tremendous changes in the past decade [1]. Immunotherapy based on the programmed death 1 (PD-1) pathway has been effective for advanced melanoma, the overall objective response rate has been around 33% in recent clinical studies [2], suggesting that a majority of melanoma patients may need alternative treatment strategies. CAP has been increasingly used in novel therapies for the treatment of cancer, wounds, and other disorders over the past two decades [5] by producing reactive oxygen species (ROS), reactive nitrogen species (RNS), electrons and ions, photons, and a transient electric field [6,7]. CAP in flowing argon was found to be efficacious in reducing head and neck tumors in human patients and improving their quality of life in a pilot study via Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

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