Material basis and potential mechanism of Baiqucai(Chelidonii Herba)in treating nasopharyngeal carcinoma based on network pharmacology,molecular docking,and experimental research
Objective To predict the action targets and mechanism of Baiqucai(Chelidonii Herba)against nasopharyngeal carcinoma(NPC)by network pharmacology and molecular docking techniques,and to verify the effects of its main active ingredients on the proliferation and apoptosis of NPC cells through experiments.Methods Through the online platforms of TCMSP,ETCM,and BATMAN-TCM,the chemical constituents and action targets of Baiqucai(Chelidonii Herba)were searched.The relevant targets of NPC were retrieved through the GEO database,and the intersection targets of Baiqucai(Chelidonii Herba)and NPC were analyzed by Shengxin online tool.STRING was used to build a protein-protein interaction(PPI)network of the common targets,and Cytoscape 3.7.1 was used to obtain core targets.GO function and KEGG pathway enrichment analyses were performed by R software programming.The condition of binding between the core targets and the main active ingredients was analyzed by molecular docking.Experimental verification:(1)5-8F cells were divided into solvent control,sanguinarine(2.5 μmol·L-1,5 μmol·L-1),chelerythrine(2.5 μmol·L-1,5 μmo·l L-1),and cisplatin 4 μg·mL-1 groups;MTT was used to test the effects of the main active ingredients of Baiqucai(Chelidonii Herba)on the proliferation of NPC cells.(2)5-8F cells were divided into solvent control,sanguinarine 5 μmol·L-1,chelerythrine 5 μmo·l L-1,and cisplatin 4 μg·mL-1 groups;apoptosis was determined by Annexin-V FITC/PI double fluorescence staining;Western blot was used to measure the effects of the main active ingredients on the proliferation,apoptosis,as well as the key proteins of mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathways of NPC cells.Results A total of 37 main active ingredients and 1 419 action targets of Baiqucai(Chelidonii Herba)were obtained.A total of 7 852 NPC disease genes were collected by searching the GEO database.There were 327 intersection targets between Baiqucai(Chelidonii Herba)and NPC,among which ten core target genes were EGFR,TP53,VEGFA,TNF,FN1,MMP9,JUN,FGF2,LYN,and F2.GO analysis mainly involved ubiquitin protein ligase binding,ubiquitin-like protein ligase binding,sulfur compound binding,integrin binding,heparin binding,and glycosaminoglycan binding.KEGG analysis mainly involved MAPK and PI3K/AKT signaling pathways.Molecular docking showed that the core targets had good binding ability with corresponding active ingredients.The experimental verification showed that compared with the solvent control group,sanguinarine and chelerythrine significantly reduced the relative proliferation rate of NPC cells(P＜0.01),increased the apoptosis rate(P＜0.01),and decreased the protein expression levels of XIAP,PCNA,ERK1/2,and AKT in 5-8F cells(P＜0.05 or P＜0.01).Conclusion Baiqucai(Chelidonii Herba)can play an anti-NPC role through multi-component,multi-target,and multi-pathway,and it has been verified by experiments that sanguinarine and chelerythrine can both inhibit the proliferation of NPC cells and induce apoptosis,the mechanism of which may be related to MAPK and PI3K/AKT signaling pathways.
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维普
