Ming Huiyun, Lu Tingting, Zhou Han, Song Wencheng, Dai Haiming
College of Basic Medical, Anhui Medical University, Hefei, 230032, China.
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health & Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.
Mol Biol Rep. 2024 Dec 7;52(1):37. doi: 10.1007/s11033-024-10132-4.
Non-small cell lung cancer (NSCLC) is a type of lung cancer, the incidence and mortality rate have been high, and the use of monotherapy is easy to make patients develop tolerance. Atmospheric pressure plasma (APP) is an emerging technology for killing cancer cells in recent years, and combination of berberine (BBR) mechanism has not been fully elucidated for NSCLC. The article's primary goal is to investigate the effect of combination on NSCLC and its associated characterization.
Antiproliferative effects were detected by cell viability assay and colony formation, and flow cytometry analysis of apoptosis and cycling showed that the combination synergistically induced apoptosis. Then, extracellular reactive oxygen species (ROS)levels and DCFH-DA-based kits examined intracellular ROS levels, and their effects on mitochondrial membrane potential were measured. Study reveals that co-induced apoptosis is associated with ROS accumulation. Subsequently, Western blotting (WB) detected the expression of epidermal growth factor receptor (EGFR), and the important signaling pathway proteins Ras/ERK and AKT/mTOR. Results showed that it could downregulation of EGFR protein expression and inhibit of activation of ERK/AKT signaling pathways. Simultaneous wound healing assay and epithelial-to-mesenchymal transition (EMT) marker detection were performed for the assessment of migration and EMT ability of NSCLC cells. Combination therapy inhibited migration and EMT of NSCLC cells.
The results of this study show that the combination can synergistically induce apoptosis of NSCLC by regulating ROS production. EGFR downregulation and AKT/ERK signaling pathway inhibition are linked to the synergistic effect.
非小细胞肺癌（NSCLC）是肺癌的一种类型，其发病率和死亡率一直居高不下，使用单一疗法容易使患者产生耐受性。大气压等离子体（APP）是近年来新兴的一种杀伤癌细胞的技术，黄连素（BBR）联合应用对NSCLC的作用机制尚未完全阐明。本文的主要目的是研究联合应用对NSCLC的影响及其相关特征。
通过细胞活力测定和集落形成检测抗增殖作用，流式细胞术分析细胞凋亡和细胞周期，结果表明联合应用可协同诱导细胞凋亡。然后，检测细胞外活性氧（ROS）水平，并用基于DCFH-DA的试剂盒检测细胞内ROS水平，并测定其对线粒体膜电位的影响。研究表明，联合诱导凋亡与ROS积累有关。随后，蛋白质免疫印迹法（WB）检测表皮生长因子受体（EGFR）的表达，以及重要信号通路蛋白Ras/ERK和AKT/mTOR。结果显示，其可下调EGFR蛋白表达并抑制ERK/AKT信号通路的激活。同时进行伤口愈合试验和上皮-间质转化（EMT）标志物检测，以评估NSCLC细胞的迁移和EMT能力。联合治疗抑制了NSCLC细胞的迁移和EMT。
本研究结果表明，联合应用可通过调节ROS生成协同诱导NSCLC细胞凋亡。EGFR下调和AKT/ERK信号通路抑制与协同效应有关。
