基于网络药理学探讨重楼与非小细胞肺癌相关分子机制

Molecular Mechanism of Paridis Rhizoma in the Treatment of Non-small Cell Lung Cancer Based on Network Pharmacology

目的:基于网络药理学方法筛选重楼[Paris polyphylla var.yunnanensis(Franch.)Hand.-Mazz.]的主要活性成分,预测其治疗非小细胞肺癌(NSCLC)的作用靶点及信号通路,进一步探讨其治疗NSCLC的可能作用机制。方法:通过中药与化学成分数据库、瑞士生物信息研究所平台(SIB)及文献挖掘,检索并收集重楼的活性成分及其对应的靶标基因。利用GeneCards、在线人类孟德尔遗传数据库(OMIM)获得NSCLC的潜在靶标基因。将二者靶标基因相映射筛选核心靶标基因,依托DAVID数据库对重楼的作用靶标基因进行基因本体(GO)富集分析生物学过程和京都基因和基因组百科全书(KEGG)通路富集注释分析,并通过分子对接验证预测结果。结果:共筛选得到重楼的7个活性成分,包括β-蜕皮素、γ-氨基丁酸、重楼皂苷A、重楼皂苷G、重楼皂苷F、重楼皂苷D、重楼皂苷B等;筛选出核心靶点7个,包括MAPK1、MAPK3、VEGFA、PIK3CA、BCL2L1、FGF1、STAT3。结论:7个核心靶点主要通过癌症通路、非小细胞肺癌通路、PI3K-AKT信号通路、FoxO信号通路、MAPK信号通路起到抗癌、免疫调节、维持端粒稳定的作用。本研究基于网络药理学的方法预测了重楼治疗NSCLC可能的作用机制,为后续的深入研究提供了参考。

Objective:To screen out the main active components of Paridis Rhizoma[dried rhizome of Paris polyphylla var.yunnanensis(Franch.)Hand.-Mazz.]based on network pharmacology,predict the targets and signaling pathways in the treatment of non-small cell lung cancer(NSCLC),so as to decipher the possible mechanism of Paridis Rhizoma in treating NSCLC.Methods:From the Database of Chinese Medicine and Chemical Constituents,Swiss Institute of Bioinformatics(SIB),and relevant literature,the active components and corresponding targets of Paridis Rhizoma were extracted.GeneCards and Online Mendelian Inheritance in Man(OMIM)were used to obtain potential target genes of NSCLC.The common targets shared by Paridis Rhizoma and NSCLC were intersected as the key targets.The gene ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the key targets were carried out based on DAVID,and the predicted results were verified by molecular docking.Results:Seven active components of Paridis Rhizoma were screened out,including β-ecdysone,γ-aminobutyric acid,polyphyllin A,polyphyllin G,polyphyllin F,polyphyllin D,and polyphyllin B.Seven key targets were screened out,including MAPK1,MAPK3,VEGFA,PIK3 CA,BCL2 L1,FGF1,and STAT3.Conclusion:The seven key targets play an important role in cancer treatment,immune regulation,and telomere stability through cancer pathway,NSCLC pathway,PI3 K-AKT signaling pathway,FoxO signaling pathway,and MAPK signaling pathway.Based on the method of network pharmacology,this study predicted the possible mechanism of Paridis Rhizoma in the treatment of NSCLC and provided reference for further research.