大戟 (EHH) 是一种具有多种药理作用的关键治疗剂。然而，对其药理特性和抗肿瘤机制的了解还存在很大差距。本研究旨在通过探索 EHH 的药理学特性、确定 NSCLC 治疗相关蛋白靶点并阐明 EHH 如何诱导 NSCLC 细胞线粒体破坏，从而弥补这一空白，从而为新型 NSCLC 治疗策略提供见解。利用字符串数据库来探索蛋白质-蛋白质相互作用。随后，单细胞分析和多组学进一步揭示了EHH靶向基因对NSCLC免疫微环境的影响，以及对免疫治疗反应的影响。最后，体内和体外实验阐明了 EHH 的抗肿瘤机制，特别是通过评估线粒体 ROS 水平和线粒体膜电位的变化。 EHH 通过与 10 个基因簇结合发挥影响，其中包括凋亡基因 CASP3。这种对 NSCLC 内免疫环境的调节影响有望成为预测免疫治疗反应的指标。此外，EHH 表现出诱导 NSCLC 细胞中线粒体 ROS 生成和线粒体膜电位扰动的能力，最终导致线粒体功能障碍和随后的肿瘤细胞凋亡。 EHH 诱导 NSCLC 细胞线粒体破坏，导致细胞凋亡，从而抑制 NSCLC 的进展。© 2024 作者。细胞与分子医学基金会和约翰·威利出版的《细胞与分子医学杂志》

Euphorbiae Humifusae Herba (EHH) is a pivotal therapeutic agent with diverse pharmacological effects. However, a substantial gap exists in understanding its pharmacological properties and anti-tumour mechanisms. This study aimed to address this gap by exploring EHH's pharmacological properties, identifying NSCLC therapy-associated protein targets, and elucidating how EHH induces mitochondrial disruption in NSCLC cells, offering insights into novel NSCLC treatment strategies. String database was utilized to explore protein-protein interactions. Subsequently, single-cell analysis and multi-omics further unveiled the impact of EHH-targeted genes on the immune microenvironment of NSCLC, as well as their influence on immunotherapeutic responses. Finally, both in vivo and in vitro experiments elucidated the anti-tumour mechanisms of EHH, specifically through the assessment of mitochondrial ROS levels and alterations in mitochondrial membrane potential. EHH exerts its influence through engagement with a cluster of 10 genes, including the apoptotic gene CASP3. This regulatory impact on the immune milieu within NSCLC holds promise as an indicator for predicting responses to immunotherapy. Besides, EHH demonstrated the capability to induce mitochondrial ROS generation and perturbations in mitochondrial membrane potential in NSCLC cells, ultimately leading to mitochondrial dysfunction and consequent apoptosis of tumour cells. EHH induces mitochondrial disruption in NSCLC cells, leading to cell apoptosis to inhibit the progress of NSCLC.© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.