摘要
目的:运用网络药理学对“石见穿-猫爪草”药对治疗肺癌的分子生物学机制进行探讨。方法:石见穿、猫爪草中具有抗肺癌活性的有效成分通过检索TCMSP及查找文献经筛选后获得。药物靶点通过查找DrugBank获得,并经UniProt校正为标准基因名称,再利用SwissTargetPrediction预测药物靶点以补充。肺癌相关基因通过检索GeneCards、OMIM、DrugBank获得。将药物作用靶点和疾病相关靶点取交集后获得药对治疗肺癌的候选基因靶点。“中药-化合物-靶点-疾病”网络借助Cytoscape构建,构建PPI网络并筛选核心网络节点在STRING上进行。GO和KEGG分析通过Metascape实现,最后构建“通路-靶点”网络,进一步筛选关键基因。结果:共获石见穿有效成分16个、猫爪草有效成分18个,候选靶点共164个,GO功能2443个和KEGG通路170条。结论:“石见穿-猫爪草”药对治疗肺癌的有效成分为槲皮素、熊果酸、β-谷甾醇和咖啡酸等;关键靶点为MAPK1、AKT1、PIK3R1、RAF1和EGFR;GO主要包括细胞因子、氧化应激、质膜传递、蛋白激酶的结合与活性、细胞凋亡;KEGG包括癌症途径、非小细胞肺癌途径和小细胞肺癌途径,还涉及EGFR酪氨酸激酶抑制剂耐药、IL-17、TNF、PI3K-Akt和凋亡等信号通路。本研究揭示了“石见穿-猫爪草”治疗肺癌的分子生物学机制,推测潜在靶点影响多条信号通路最终拮抗肺癌细胞的增殖、分化、侵袭、转移及促进凋亡,为进一步的基础研究提供依据。
Objective:To explore the molecular biological mechanism of the"Salvia chinensis and Radix Ranunculi Ternati"drug pair in the treatment of lung cancer based on network pharmacology.Methods:The TCMSP database was searched to screen the active compounds which resist lung cancer activity in Salvia chinensis and Radix Ranunculi Ternati.The candidate compounds were unified in the DrugBank to find the corresponding drug targets which were corrected to the standard gene names by the UniProt database.The SwissTargetPrediction platform was used to predict other targets.GeneCards,OMIM and DrugBank were searched to obtain genes related to lung cancer.After taking the intersection,the candidate gene target of drug pair in the treatment of lung cancer could be obtained.The"herbs-compounds-targets-disease"network was bulit with Cytoscape,and the PPI network was bulit on the STRING platform while the core network nodes were screened.GO and KEGG analysis on candidate genes was implemented through Metacape platform,and a"pathways-targets"network was bulit to further screen key genes.Results:A total of 16 active compounds in Salvia chinensis,18 active compounds in Radix Ranunculi Ternati,164 candidate targets,2443 GO functions and 170 KEGG pathways were obtained.Conclusion:The effective compounds of"Salvia chinensis and Radix Ranunculi Ternati"drug pair in the treatment of lung cancer are quercetin,ursolic acid,β-sitosterol and caffeic acid.The key targets are MAPK1,AKT1,PIK3R1,RAF1 and EGFR.GO functions mainly include cytokines,oxidative stress,plasma membrane transmission,protein kinase binding and activity,apoptosis.KEGG could directly regulate pathways in cancer,non-small cells lung cancer pathway and small cell lung cancer pathway.KEGG also involves EGFR tyrosine kinase inhibitor resistance,IL-17,TNF,PI3K-AKT signaling pathway and apoptosis.This study reveals the molecular biological mechanism of"Salvia chinen⁃sis and Radix Ranunculi Ternati"drug pair in the treatment of lung cancer.It is reasoned that its potential targets
作者
胡佳奇
许博文
程孟祺
赵雨薇
张兴
郑红刚
花宝金
HU Jia-qi;XU Bo-wen;CHENG Meng-qi;ZHAO Yu-wei;ZHANG Xing;ZHENG Hong-gang;HUA Bao-jin(Beijing University of Chinese Medicine,Beijing 100029,China;Department of Oncology,Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)
出处
《海南医学院学报》
CAS
2022年第11期860-869,共10页
Journal of Hainan Medical University
基金
国家自然科学基金面上项目(81673961)
北京市自然科学基金项目(7172186)
中国中医科学院优秀青年科技人才(创新类)培养专项(ZZ13-YQ-028)。
关键词
“石见穿-猫爪草”药对
肺癌
网络药理学
"Salvia chinensis and Radix Ranunculi Ternati"drug pair
Lung cancer
Network pharmacology
