冷大气等离子体通过减少谷胱甘肽合成来抑制癌症增殖。

The Cold Atmospheric Plasma Inhibits Cancer Proliferation Through Reducing Glutathione Synthesis.

作者信息

Yang Qiyu, Zhao Wei, Yang Lingling, Fan Yongqin, Shao Changsheng, Wang Tao, Zhang Fengqiu

机构信息

School of Physics and Laboratory of Zhongyuan Light, Zhengzhou University, Zhengzhou 450001, China.

Henan Key Laboratory of Ion-Beam Green Agriculture Bioengineering, Zhengzhou University, Zhengzhou 450001, China.

出版信息

Molecules. 2025 Jun 30;30(13):2808. doi: 10.3390/molecules30132808.

DOI:10.3390/molecules30132808

PMID:40649322

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12251158/

Abstract

(1) Objective: Cold atmospheric plasma (CAP) is a safe and effective alternative to radiotherapy for cancer treatment. Its anticancer effects are attributed to increased intracellular reactive oxygen species (ROS). Glutathione, a key antioxidant derived from glutamine, is critical for cell proliferation. This study investigated whether CAP-induced ROS elevation results from reduced glutamine-glutathione conversion and elucidates the underlying mechanisms. (2) Methods: Using esophageal squamous carcinoma cell models (Ec9706 and Eca109), we analyzed CAP's effects on key enzymes in glutamine metabolism (Glutaminase 1 and γ-glutamylcysteine ligase) and proliferation-related genes (e.g., Retinoblastoma and Nuclear respiratory factor 2). Transcriptome analysis further explored molecular pathways involved in CAP-mediated anticancer effects. (3) Results: CAP reduced Glutaminase 1 and γ-glutamylcysteine ligase expression, leading to lower intracellular glutathione, higher ROS activity, and enhanced apoptosis. Transcriptome data confirmed CAP's role in oxidation-reduction reactions and glutamine metabolism. (4) Conclusions: This study provides the first mechanistic insights into CAP's anticancer effects by targeting glutamine metabolism. While based on in vitro assays, these findings guide the development of novel CAP therapies for currently incurable cancers.

摘要

(1) 目的：冷大气等离子体（CAP）是癌症治疗中放疗的一种安全有效的替代方法。其抗癌作用归因于细胞内活性氧（ROS）增加。谷胱甘肽是一种源自谷氨酰胺的关键抗氧化剂，对细胞增殖至关重要。本研究调查了CAP诱导的ROS升高是否源于谷氨酰胺-谷胱甘肽转化减少，并阐明其潜在机制。(2) 方法：使用食管鳞状癌细胞模型（Ec9706和Eca109），我们分析了CAP对谷氨酰胺代谢关键酶（谷氨酰胺酶1和γ-谷氨酰半胱氨酸连接酶）以及增殖相关基因（如视网膜母细胞瘤和核呼吸因子2）的影响。转录组分析进一步探索了CAP介导的抗癌作用所涉及的分子途径。(3) 结果：CAP降低了谷氨酰胺酶1和γ-谷氨酰半胱氨酸连接酶的表达，导致细胞内谷胱甘肽水平降低、ROS活性升高以及细胞凋亡增强。转录组数据证实了CAP在氧化还原反应和谷氨酰胺代谢中的作用。(4) 结论：本研究首次通过靶向谷氨酰胺代谢对CAP的抗癌作用提供了机制性见解。虽然基于体外试验，但这些发现为目前无法治愈的癌症开发新型CAP疗法提供了指导。