基于网络药理学探讨白藜芦醇治疗肺癌的生物分子机制

Biomolecular Mechanism of Resveratrol Against Lung Cancer Based on Network Pharmacology

目的基于网络药理学,运用在线数据库研究白藜芦醇治疗肺癌的潜在作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、PubChem、Swiss TargetPrediction、GeneCards数据库分别获取白藜芦醇和肺癌的相关基因,取二者交集基因,使用String数据库获得交集基因的蛋白相互作用(PPI)网络图,使用DAVID6.8对交集基因进行GO和KEGG富集分析。采用Cytoscape3.7.2软件构建化合物-靶点-通路-疾病网络模型。使用AutoDock4.2.6软件对白藜芦醇和重要靶点进行分子对接。Western blot检测白藜芦醇对人肺癌H1975细胞p-Akt蛋白表达的影响。结果获得白藜芦醇和肺癌交集基因78个,PPI网络图表明交集基因关系密切。富集分析得到生物过程55项、分子功能26项、细胞组分18项,以及86条相关通路,其中以PI3K-Akt通路富集靶点较多。分子对接结果显示,白藜芦醇与PIK3CB、PIK3CA这2个重要靶点均能稳定结合。Western blot检测结果显示,白藜芦醇能够显著降低人肺癌H1975细胞p-Akt蛋白表达。结论白藜芦醇可能主要通过作用于PIK3CB、PIK3CA靶点,介导PI3K-Akt信号通路发挥治疗肺癌作用。

Objective To use the online databases to study the potential mechanism of resveratrol in treating lung cancer based on network pharmacology. Methods The genes related to resveratrol and lung cancer were obtained from TCMSP, PubChem, SwissTargetPrediction and GeneCards database, and the related intersection genes of resveratrol and lung cancer were screened out. The String database was used to draw the PPI network diagram of the intersection genes, and the DAVID 6.8 was used to perform GO and KEGG enrichment analysis. The compound-target-signal pathway-disease network model was constructed by using Cytoscape 3.7.2 software. AutoDock 4.2.6 software was used to perform molecular docking of resveratrol and important targets. Western blot was used to detect the effect of resveratrol on the expression of p-Akt protein in human lung cancer H1975 cell line. Results Totally 78 intersection genes of resveratrol and lung cancer were obtained, and the PPI network diagram showed that there was a close relationship between them. The enrichment analysis mainly obtained 55 biological processes, 26 molecular functions, 18 cellular components, and 86 related pathways, among which the PI3K-Akt pathway enriched the most targets. Molecular docking results showed that resveratrol could stably bind to two important targets, PIK3CB and PIK3CA. Western blot test results showed that resveratrol could significantly reduce the expression of p-Akt protein in human lung cancer H1975 cells. Conclusion Resveratrol may mainly act on the targets of PIK3CB and PIK3CA, and mediates the PI3K-Akt signaling pathway to exert anti-lung cancer action.