Mao Yun, Peng Xi, Xue Peng, Lu Dianrong, Li Linlu, Zhu Shijie
Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.
Department of Oncology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China.
Evid Based Complement Alternat Med. 2020 Feb 17;2020:1246742. doi: 10.1155/2020/1246742. eCollection 2020.
Cinobufotalin injection, extracted from the skin of Chinese giant salamander or black sable, has good clinical effect against lung cancer. However, owing to its complex composition, the pharmacological mechanism of cinobufotalin injection has not been fully clarified. This study aimed to explore the mechanism of action of cinobufotalin injection against lung cancer using network pharmacology and bioinformatics. Compounds of cinobufotalin injection were determined by literature retrieval, and potential therapeutic targets of cinobufotalin injection were screened from Swiss Target Prediction and STITCH databases. Lung-cancer-related genes were summarized from GeneCards, OMIM, and DrugBank databases. The pharmacological mechanism of cinobufotalin injection against lung cancer was determined by enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network was constructed. We identified 23 compounds and 506 potential therapeutic targets of cinobufotalin injection, as well as 70 genes as potential therapeutic targets of cinobufotalin injection in lung cancer by molecular docking. The antilung cancer effect of cinobufotalin injection was shown to involve cell cycle, cell proliferation, antiangiogenesis effect, and immune inflammation pathways, such as PI3K-Akt, VEGF, and the Toll-like receptor signaling pathway. In network analysis, the hub targets of cinobufotalin injection against lung cancer were identified as VEGFA, EGFR, CCND1, CASP3, and AKT1. A network diagram of "drug-compounds-target-pathway" was constructed through network pharmacology to elucidate the pharmacological mechanism of the antilung cancer effect of cinobufotalin injection, which is conducive to guiding clinical medication.
华蟾素注射液提取自中国大鲵或紫貂的皮肤，对肺癌具有良好的临床疗效。然而，由于其成分复杂，华蟾素注射液的药理机制尚未完全阐明。本研究旨在运用网络药理学和生物信息学方法探索华蟾素注射液抗肺癌的作用机制。通过文献检索确定华蟾素注射液的化合物，从瑞士靶点预测数据库和STITCH数据库中筛选华蟾素注射液的潜在治疗靶点。从基因卡片数据库、在线人类孟德尔遗传数据库和药物银行数据库中总结肺癌相关基因。通过基因本体富集分析和京都基因与基因组百科全书分析确定华蟾素注射液抗肺癌的药理机制，并构建蛋白质-蛋白质相互作用网络。通过分子对接，我们确定了华蟾素注射液的23种化合物和506个潜在治疗靶点，以及70个作为华蟾素注射液在肺癌中的潜在治疗靶点的基因。结果表明，华蟾素注射液的抗肺癌作用涉及细胞周期、细胞增殖、抗血管生成作用以及免疫炎症途径，如PI3K-Akt、VEGF和Toll样受体信号通路。在网络分析中，华蟾素注射液抗肺癌的核心靶点被确定为VEGFA、EGFR、CCND1、CASP3和AKT1。通过网络药理学构建了“药物-化合物-靶点-途径”网络图，以阐明华蟾素注射液抗肺癌作用的药理机制，这有助于指导临床用药。
