Yang Zhirui, Wu Mingquan, Zhou Xin, Luo Jin, Liu Yi, Li Lin
Department of Nuclear Medicine, Chengdu Second People's Hospital, Chengdu, Sichuan, China.
Department of Pharmacy, Sichuan Orthopedic Hospital, Chengdu, Sichuan, China.
Medicine (Baltimore). 2025 May 9;104(19):e42366. doi: 10.1097/MD.0000000000042366.
Non-small cell lung cancer (NSCLC) poses a significant threat to public health worldwide. Curcumae Rhizoma (CR) has potent therapeutic potential in different cancers. However, the mechanism of CR treating NSCLC remains unclear. In this study, a network pharmacology-based strategy is followed to address the issue. The targets related to CR or NSCLC were obtained from multiple online public databases. Compound-target network was constructed using Cytoscape. Protein-protein interaction (PPI) was analyzed by STRING. Key transcription factors were explored in TRRUST. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were accomplished in Metascape. The druglikeness of compounds was tested in Molinspiration Cheminformatics Software. Autodock Vina was used for molecular docking. Molecular dynamic (MD) simulation was performed using Gromacs. There were 104 overlapped targets considered as key targets of CR treating NSCLC. The key components of CR, including reynosin, (4S,5S)-13-hydroxygermacrone 4,5-epoxide, and (E)-1,7-bis(4-hydroxyphenyl)-6-hepten-3-one, were screened by topological parameters and bioactivity scores. Central clustered targets in PPI network (epidermal growth factor receptor [EGFR], SRC, JAK2, and mitogen-activated protein kinase 3 [MAPK3]) were identified as critical therapeutic targets of CR. GO and KEGG enrichment analysis suggested that therapeutic effect of CR on NSCLC involved various biological processes, cellular components, and molecular functions, and pathways in cancer, JAK-STAT signaling pathway, and p53 signaling pathway were strongly related. Molecular docking and MD simulation suggested that key compounds in CR had high binding affinity to critical NSCLC targets, like EGFR, JAK2, SRC, and MAPK3, with stable complexes formed. This study revealed key components and mechanism of CR treating NSCLC based on a network pharmacology-driven strategy, providing a reference for in-depth study on treating NSCLC.
非小细胞肺癌（NSCLC）对全球公共卫生构成重大威胁。莪术在不同癌症中具有强大的治疗潜力。然而，莪术治疗NSCLC的机制仍不清楚。在本研究中，采用基于网络药理学的策略来解决这一问题。从多个在线公共数据库中获取与莪术或NSCLC相关的靶点。使用Cytoscape构建化合物-靶点网络。通过STRING分析蛋白质-蛋白质相互作用（PPI）。在TRRUST中探索关键转录因子。在Metascape中完成基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析。在Molinspiration化学信息学软件中测试化合物的类药性质。使用Autodock Vina进行分子对接。使用Gromacs进行分子动力学（MD）模拟。有104个重叠靶点被视为莪术治疗NSCLC的关键靶点。通过拓扑参数和生物活性评分筛选出莪术的关键成分，包括雷琐辛、（4S，5S）-13-羟基吉马酮4,5-环氧化物和（E）-1,7-双（4-羟基苯基）-6-庚烯-3-酮。PPI网络中的中心聚集靶点（表皮生长因子受体[EGFR]、SRC、JAK2和丝裂原活化蛋白激酶3[MAPK3]）被确定为莪术的关键治疗靶点。GO和KEGG富集分析表明，莪术对NSCLC的治疗作用涉及各种生物学过程、细胞成分和分子功能，且癌症通路、JAK-STAT信号通路和p53信号通路密切相关。分子对接和MD模拟表明，莪术中的关键化合物与关键NSCLC靶点（如EGFR、JAK2、SRC和MAPK3）具有高结合亲和力，并形成稳定的复合物。本研究基于网络药理学驱动的策略揭示了莪术治疗NSCLC的关键成分和机制，为深入研究NSCLC的治疗提供了参考。
