瓜蒌-浙贝母抗肺腺癌作用机制的网络药理学预测与实验验证
Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma.
作者信息
Zhao Xu-Yi, Yang Yun-Yue, Feng Jing-Li, Feng Cui-Ling
机构信息
Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine.
Traditional Chinese Medicine Department, Peking University People's Hospital;
出版信息
J Vis Exp. 2023 Mar 3(193). doi: 10.3791/64847.
We aimed to study the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma (LUAD) based on network pharmacology and experimental verification. The effective components and potential targets of Trichosanthis and Fritillaria thunbergii were collected by high-throughput experiment and reference-guided (HERB) database of traditional Chinese medicine and a similarity ensemble approach (SEA) database, and the LUAD-related targets were queried by the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. A drug-component-disease-target network was constructed by Cytoscape software. Protein-protein interaction (PPI) network, gene ontology (GO) function, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to obtain core targets and key pathways. An aqueous extract of Trichosanthes-Fritillaria thunbergii and A549 cells were used for the subsequent experimental validation. Through the HERB database and literature search, 31 effective compounds and 157 potential target genes of Trichosanthes-Fritillaria thunbergii were screened, of which 144 were regulatory targets of Trichosanthes-Fritillaria thunbergii in the treatment of lung adenocarcinoma. The GO functional enrichment analysis showed that the mechanism of action of Trichosanthes-Fritillaria thunbergii against lung adenocarcinoma is mainly protein phosphorylation. The KEGG pathway enrichment analysis suggested that the treatment of lung adenocarcinoma by Trichosanthes-Fritillaria thunbergii mainly involves the PI3K/AKT signaling pathway. The experimental validation showed that an aqueous extract of Trichosanthes-Fritillaria thunbergii could inhibit the proliferation of A549 cells and the phosphorylation of AKT. Through network pharmacology and experimental validation, it was verified that the PI3K/AKT signaling pathway plays a vital role in the action of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma.
我们旨在基于网络药理学和实验验证研究瓜蒌贝母治疗肺腺癌（LUAD）的机制。通过高通量实验以及中药参考导向（HERB）数据库和相似性整合方法（SEA）数据库收集瓜蒌和浙贝母的有效成分及潜在靶点，并通过基因卡片（GeneCards）和人类孟德尔遗传在线（OMIM）数据库查询LUAD相关靶点。利用Cytoscape软件构建药物-成分-疾病-靶点网络。进行蛋白质-蛋白质相互作用（PPI）网络、基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析以获得核心靶点和关键通路。随后使用瓜蒌贝母水提取物和A549细胞进行实验验证。通过HERB数据库和文献检索，筛选出瓜蒌贝母的31种有效化合物和157个潜在靶基因，其中144个是瓜蒌贝母治疗肺腺癌的调控靶点。GO功能富集分析表明，瓜蒌贝母抗肺腺癌的作用机制主要是蛋白质磷酸化。KEGG通路富集分析提示，瓜蒌贝母治疗肺腺癌主要涉及PI3K/AKT信号通路。实验验证表明，瓜蒌贝母水提取物可抑制A549细胞增殖及AKT磷酸化。通过网络药理学和实验验证，证实PI3K/AKT信号通路在瓜蒌贝母治疗肺腺癌的作用中起关键作用。
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