Tang Yu, Xian Zhengping, Wu Fengjiao, Cao Hongyu, Wang Lihao, Tang Qian, Du Yanan, Zheng Xuefang
College of Life and Health, Dalian University, Dalian, 116622, China.
Liaoning Key Laboratory of Bio-Organic Chemistry, Dalian University, Dalian, 116622, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan;398(1):843-854. doi: 10.1007/s00210-024-03310-5. Epub 2024 Jul 29.
In the course of clinical treatment for anti-tumor, the combination of traditional Chinese medicine (TCM) and other treatment schemes can reduce toxicity and increase efficiency. The purpose of this paper is to find out the key TCM and effective components for the treatment of non-small cell lung cancer (NSCLC) and analyze its therapeutic mechanism by analyzing the prescription of TCM combined with chemotherapy for NSCLC. Firstly, the prescriptions of TCM in the randomized controlled trials combined with chemotherapy for NSCLC were collected, and the core TCM was screened by frequency statistics, association rule analysis, and cluster analysis. Then, the intersection targets of the potential effects of NSCLC and core Chinese medicine were collected, and PPI analysis and enrichment analysis were performed on the intersection targets to screen the core targets, components, and pathways. The core components were verified by molecular docking and cell experiments. In this study, 269 prescriptions were collected, among which the frequency of medication for Astragalus membranaceus (HQ, in Chinese), Wolfiporia cocos (FL, in Chinese), and Atractylodes macrocephala (BZ, in Chinese) was over 100. Association rule analysis showed that they were highly correlated and clustered into the same category in cluster analysis. Their core components were quercetin, kaempferol, and isorhamnetin. The molecular docking results of the core components with the core targets AKT1 and EGFR obtained by PPI network analysis showed that they could bind stably. KEGG analysis screened 110 pathways including PI3K-Akt; the results of CCK-8 showed that quercetin, kaempferol, and isorhamnetin could effectively inhibit the proliferation of A549 cells, and isorhamnetin had the best inhibitory effect. Isorhamnetin can inhibit the migration and invasion of A549 cells, induce apoptosis and G1 phase arrest, and decrease the expression of P-PI3K and P-AKT in A549 cells. In a word, the key TCM for the treatment of NSCLC includes HQ, FL, and BZ. and its key components quercetin, kaempferol, and isorhamnetin have potential therapeutic effects on NSCLC according to the research results.
在抗肿瘤临床治疗过程中,中药与其他治疗方案联合应用可减毒增效。本文旨在通过分析中药联合化疗治疗非小细胞肺癌(NSCLC)的方剂,找出治疗NSCLC的关键中药及其有效成分,并分析其治疗机制。首先,收集NSCLC化疗联合随机对照试验中的中药方剂,通过频次统计、关联规则分析和聚类分析筛选核心中药。然后,收集NSCLC与核心中药潜在作用的交集靶点,对交集靶点进行蛋白质-蛋白质相互作用(PPI)分析和富集分析,以筛选核心靶点、成分和通路。通过分子对接和细胞实验对核心成分进行验证。本研究共收集269首方剂,其中黄芪、茯苓、白术用药频次均超过100次。关联规则分析表明它们相关性高,聚类分析中聚为同一类。其核心成分为槲皮素、山奈酚和异鼠李素。通过PPI网络分析得到的核心成分与核心靶点AKT1和表皮生长因子受体(EGFR)的分子对接结果显示它们能稳定结合。京都基因与基因组百科全书(KEGG)分析筛选出包括磷脂酰肌醇-3激酶-蛋白激酶B(PI3K-Akt)等在内的110条通路;细胞计数试剂盒-8(CCK-8)结果显示,槲皮素、山奈酚和异鼠李素能有效抑制人肺癌细胞系A549细胞增殖,异鼠李素抑制作用最佳。异鼠李素可抑制A549细胞迁移和侵袭,诱导细胞凋亡及G1期阻滞,并降低A549细胞中磷酸化PI3K(P-PI3K)和磷酸化蛋白激酶B(P-AKT)的表达。总之,治疗NSCLC的关键中药包括黄芪、茯苓和白术,根据研究结果,其关键成分槲皮素、山奈酚和异鼠李素对NSCLC具有潜在治疗作用。