Investigating the Mechanism of Action and Key Signaling Pathways of Shengxian Decoction in Lung Cancer Using Network Pharmacology,Molecular Docking
Objective:To investigate the active components,target points,and potential mechanisms of Shengxian Decoction(SXT)in the intervention of lung cancer using network pharmacology,molecular docking and in vitro experiments.Methods:Compounds of SXT were screened through the TCMSP database and literature review,while lung cancer-related targets were obtained from GeneCards,OMIM,and Drugbank databases.A"SXT-active component-potential target"network was constructed using Cytoscape,and key com-pounds were identified through topological analysis.The PPI network of SXT-lung cancer targets was built using STRING,and the core targets of SXT were identified by MCODE cluster.Metascape was used for GO functional analysis and KEGG pathway enrichment anal-ysis of the core targets.Molecular docking validation was performed using Autodock.The effect of SXT serum on proliferation,inva-sion,and apoptosis of human lung adenocarcinoma A549 cells was measured,and the expression of key pathway genes and proteins was detected using Western blot and qRT-PCR.Results:76 active components of SXT were identified,interacting with 142 lung cancer-re-lated targets.The main active components were quercetin,kaempferol,stigmasterol,luteolin,and isorhamnetin.PPI analysis identi-fied 20 core targets including AKT1,IL-6,VEGFA,JUN,and IL-1β.GO and KEGG pathway enrichment analyses suggested that the anti-lung cancer mechanism of SXT involves cell apoptosis,cell proliferation,cell cycle,DNA transcription,PI3K-Akt,NF-κB,and VEGF signaling pathways.Molecular docking and molecular dynamics simulation studies demonstrated strong binding force and stability between these compounds and AKT1.In vitro experiments showed that SXT can effectively inhibit the proliferation and invasion of A549 cells and promote their apoptosis.RT-qPCR results indicated that SXT serum at high,medium,and low doses significantly downregulated the expression of PI3K and AKT mRNA(P<0.01)compared to the control group.Western blot results showed that the high-dose SXT serum group significantly reduced the expression levels of p-PI3K and p-AKT proteins in A549 cells(P<0.01).Con-clusion:SXT may exert an anti-lung cancer effect by regulating the PI3K/Akt signaling pathway,effectively inhibiting the proliferation and invasion of lung cancer cells and promoting their apoptosis,providing a reference for subsequent mechanism verification and clini-cal application.
Shengxian decoctionLung cancerMechanism of actionNetwork pharmacologyMolecular docking
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维普
