Xu L, Huang F, Zhang Y, Niu W, Pang J, Li S, Li X
Bengbu Medical College, Bengbu 233030, China.
Key Laboratory of Anhui Province for New Technology of Chinese Medicine Decoction Pieces Manufacturing, Bozhou 236800, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2021 Aug 31;41(9):1319-1328. doi: 10.12122/j.issn.1673-4254.2021.09.05.
To explore the molecular mechanism mediating the inhibitory effect of against brain metastasis of lung cancer using network pharmacology methods and molecular docking.
The chemical components of and their targets were obtained through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The relevant targets for brain metastasis of lung cancer were screened using the GeneCards database. Clusterpro-filerR package was used to perform GO and KEGG enrichment analysis. Cytoscape and STRING database were used to construct the "active ingredient-target-disease" network and protein-protein interaction (PPI) network of . The core components of and their targets in the treatment of lung cancer brain metastasis were screened based on the topological parameters, and the results were verified using molecular docking and in Chuanxiong extract- treated human lung cancer PC9 cells by detecting the core target with Western blotting.
Forty-eight active ingredients of including (Z)-ligustilide, butylphthalide, oleic acid, and myricetone were screened, which target 49 proteins including INS, BDNF, FOS, VEGFA, PTGS2, ESR1, MAPK14, and PTGS1. These proteins participated in 57 biological functions such as nuclear receptor activity, ligand activation, and transcription factor activity, involving 40 signaling pathways such as prolactin signaling pathway, breast cancer, and etrogen signaling. The results of molecular docking showed that myricetone, butylphthalide, 4-hydroxy-3 butylphthalide, (Z)-ligustilide, and ligustalide-E, among others, had strong affinities to 7 cores targets including BDNF, FOS, PTGS2, and MAPK14. In PC9 cells, treatment with extract resulted in significant reductions in the phosphorylation levels of PI3K, Akt and VEGF ( < 0.01).
contains multiple active ingredients against brain metastasis lung cancer, and these ingredients act on multiple targets involving multiple signal pathways and biological functions.
运用网络药理学方法和分子对接技术，探讨[具体药物名称未给出]对肺癌脑转移抑制作用的分子机制。
通过中药系统药理学（TCMSP）数据库获取[具体药物名称未给出]的化学成分及其靶点。利用GeneCards数据库筛选肺癌脑转移的相关靶点。使用ClusterprofilerR软件包进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。运用Cytoscape软件和STRING数据库构建[具体药物名称未给出]的“活性成分-靶点-疾病”网络和蛋白质-蛋白质相互作用（PPI）网络。基于拓扑参数筛选[具体药物名称未给出]治疗肺癌脑转移的核心成分及其靶点，并通过分子对接以及用川芎提取物处理人肺癌PC9细胞，采用蛋白质免疫印迹法检测核心靶点来验证结果。
筛选出[具体药物名称未给出]的48种活性成分，包括（Z）-藁本内酯、丁苯酞、油酸和杨梅酮，它们作用于49种蛋白质，如胰岛素（INS）、脑源性神经营养因子（BDNF）、原癌基因c-Fos（FOS）、血管内皮生长因子A（VEGFA）、环氧合酶-2（PTGS2）、雌激素受体1（ESR1）、丝裂原活化蛋白激酶14（MAPK14）和环氧合酶-1（PTGS1）。这些蛋白质参与57种生物学功能，如核受体活性、配体激活和转录因子活性，涉及40条信号通路，如催乳素信号通路、乳腺癌和雌激素信号通路。分子对接结果表明，杨梅酮、丁苯酞、4-羟基-3-丁苯酞、（Z）-藁本内酯和藁本内酯-E等对包括BDNF、FOS、PTGS2和MAPK14在内的7个核心靶点具有较强亲和力。在PC9细胞中，用川芎提取物处理导致磷脂酰肌醇-3激酶（PI3K）、蛋白激酶B（Akt）和血管内皮生长因子（VEGF）的磷酸化水平显著降低（P<0.01）。
[具体药物名称未给出]含有多种抗肺癌脑转移的活性成分，这些成分作用于多个靶点，涉及多个信号通路和生物学功能。
