摘要
目的基于网络药理学及体外实验探讨复方苦参注射液(CKI)抗非小细胞肺癌(NSCLC)的分子机制。方法通过网络公开数据库及查阅文献,分别获得CKI和NSCLC的靶点。筛选两者共有靶点后,构建靶点蛋白互作网络,进而找到CKI抗NSCLC的关键靶点。利用David数据库对关键靶点进行GO和KEGG信号通路分析,通过R软件对结果进行可视化。通过qPCR技术对富集到与NSCLC相关的信号通路进行体外实验验证。结果共收集到CKI相关靶点372个,NSCLC相关靶点426个。生物信息学分析共富集到93个生物过程(BP)以及30条信号通路,其中缺氧诱导因子1(HIF-1)信号通路、丝裂原活化蛋白激酶(AMPK)信号通路、磷脂酰肌醇3'-激酶(PI3KAkt)信号通路可能与CKI抗NSCLC相关。体外实验表明,经CKI治疗后,ERBB2、MTOR、IGF1R及VEGFA基因相对表达量显著降低。结论CKI可能通过抑制ERBB2、MTOR、IGF1R及VEGFA基因相对表达,进而调控HIF-1、AMPK、PI3K-Akt信号通路发挥其抗NSCLC的作用。
Objective To determine the molecular mechanism of compound Kushen injection(CKI)against non-small cell lung cancer(NSCLC)based on network pharmacology and in vitro experiments.Methods Through retrieving public database and literature review,the targets of CKI and NSCLC were obtained respectively.By screening the common targets of CKI and NSCLC,the target protein interaction network was constructed to find the key targets of CKI against NSCLC.David database was used to analyze gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for key targets.R software was used to visualize the results.Finally,qPCR was used to verify the genes enriched into NSCLC-related signaling pathways in vitro.Results Totally 372 CKI-related targets and 426 NSCLC-related targets were collected.Bioinformatics showed that 93 biological process(BP)and 30 signaling pathways were enriched,among which hypoxia-inducible factor 1(HIF-1)signaling pathway,mitogen-activated protein kinase(AMPK)signaling pathway and phosphatidylinositol 3’-kinase(PI3K-Akt)signaling pathway might be associated with CKI against NSCLC.In vitro experiments showed that the relative expression levels of ERBB2,MTOR,IGF1R and VEGFA genes were significantly decreased after the CKI treatment.Conclusion CKI may inhibit the relative expressions of ERBB2,MTOR,IGF1R and VEGFA genes to regulate HIF-1,AMPK and PI3K-Akt signaling pathway to exert its against NSCLC effect.
作者
颜渊鸳
章波
YAN Yuan-yuan;ZHANG Bo(Department of Pharmacy,The Third People's Hospital of Hainan Province,Sanya Hainan 572000;Scientific Research Center,Guilin Medical Institute,Guilin Guangxi 541199)
出处
《中南药学》
CAS
2022年第4期817-822,共6页
Central South Pharmacy
关键词
复方苦参注射液
非小细胞肺癌
网络药理学
作用机制
compound Kushen injection
non-small cell lung cancer
network pharmacology
mechanism