Geng He, Xue Yujie, Yan Binghua, Lu Zhaoxue, Yang Hengjin, Li Peng, Zhou Jundong
Department of Radiation Oncology, Huaian Hospital of Huaian City, Huaian Cancer Hospital, Huaian, Jiangsu, China.
Department of Pathology, Affiliated Huaian NO. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, China.
Biol Proced Online. 2024 Dec 31;26(1):33. doi: 10.1186/s12575-024-00259-w.
Strychni Semen, characterized by its bitter taste and warm properties, has been confirmed to possess anti-tumor properties. However, the molecular mechanism of Strychni Semen in treating non-small cell lung cancer (NSCLC) needs further study. This study aimed to explore the molecular mechanism of Strychni Semen in treating NSCLC based on network pharmacology and molecular docking. The active components and targets of Strychni Semen were retrieved from the TCMSP, supplemented by the HERB database and the related literature. NSCLC-related targets were retrieved from the GeneCards, OMIM and DisGenet databases. The intersection targets of Strychni Semen in treating NSCLC were obtained via an online platform. The Protein-Protein Interaction (PPI) network was subsequently constructed to deeply analyse the interrelationship of the intersection targets via the String database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out via the Metascape database. The interactive networks between Strychni Semen and NSCLC were constructed via Cytoscape 3.9.1. Molecular docking detected interactions between the key components and the core targets. The core targets were validated via GEO datasets. 21 active components and 67 targets were identified, with 47 associated with NSCLC. The key active components were Stigmasterol, IcarideA, 2-Hydroxymethylanthraquinone, (+)-catechin, (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one, (S)-Stylopine, Brucine and Isobrucine. The core targets were PTGS2, NR3C1, ESR1, CASP3 and PRKACA. Molecular docking revealed that these compounds undergo strong binding affinity with the core genes. GEO database indicated that PTGS2 was the most promising core target. In addition, Strychni Semen's effects on NSCLC involved mainly the Calcium pathway, the Estrogen pathway, and the cGMP-PKG and cAMP pathways. This study visually demonstrated the mechanism of the therapeutic effect of Strychni Semen in NSCLC through multiple components, targets and pathways which provides a basis for clinical treatment and further experimental research.
马钱子味极苦，性温，已证实具有抗肿瘤特性。然而，马钱子治疗非小细胞肺癌（NSCLC）的分子机制尚需进一步研究。本研究旨在基于网络药理学和分子对接技术探索马钱子治疗NSCLC的分子机制。从中药系统药理学数据库与分析平台（TCMSP）中检索马钱子的活性成分和靶点，并补充使用中药综合数据库（HERB）及相关文献。从基因卡片数据库（GeneCards）、在线孟德尔人类遗传数据库（OMIM）和疾病基因数据库（DisGenet）中检索NSCLC相关靶点。通过在线平台获取马钱子治疗NSCLC的交集靶点。随后通过String数据库构建蛋白质-蛋白质相互作用（PPI）网络，深入分析交集靶点之间的相互关系。通过Metascape数据库进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析。使用Cytoscape 3.9.1构建马钱子与NSCLC之间的相互作用网络。分子对接检测关键成分与核心靶点之间的相互作用。通过基因表达综合数据库（GEO）数据集验证核心靶点。共鉴定出21种活性成分和67个靶点，其中47个与NSCLC相关。关键活性成分有豆甾醇、淫羊藿苷A、2-羟甲基蒽醌、（+）-儿茶素、（2R）-5,7-二羟基-2-（4-羟基苯基）色满-4-酮、（S）-番荔枝碱、马钱子碱和异马钱子碱。核心靶点有环氧化酶2（PTGS2）、糖皮质激素受体（NR3C1）、雌激素受体1（ESR1）、半胱天冬酶3（CASP3）和蛋白激酶A催化亚基α（PRKACA）。分子对接显示这些化合物与核心基因具有很强的结合亲和力。GEO数据库表明PTGS2是最有前景的核心靶点。此外，马钱子对NSCLC的作用主要涉及钙信号通路、雌激素信号通路以及环磷酸鸟苷-蛋白激酶G（cGMP-PKG）和环磷酸腺苷（cAMP）信号通路。本研究通过多个成分、靶点和通路直观地展示了马钱子治疗NSCLC的作用机制，为临床治疗和进一步的实验研究提供了依据。
