ArticleChinese journal of integrative medicine2024
Network Pharmacology Based Elucidation of Molecular Mechanisms of Laoke Formula for Treatment of Advanced Non-Small Cell Lung Cancer.
Article in Chinese journal of integrative medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Traditional Chinese medicine for non-small cell lung carcinoma: An evidence mapping.Integrative medicine research · 2026Article
- Construction of a gene-metabolite-microbiome regulatory network reveals novel therapeutic targets in bladder cancer through multi-omics analysis.Annals of medicine · 2025Article
- DNA damage response and cell fate decisions across the lifespan: from fetal development to age-related respiratory diseases.Cell & bioscience · 2025Review
- Mechanism of astragaloside A against lung adenocarcinoma based on network pharmacology combined with molecular dynamics simulation technique.Scientific reports · 2025Article
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Abstract
objectiveTo explore the specific pharmacological molecular mechanisms of Laoke Formula (LK) on treating advanced non-small cell lung cancer (NSCLC) based on clinical application, network pharmacology and experimental validation.
methodsKaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of Chinese medicine (CM) treatment in 296 patients with NSCLC in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2015. The compounds of LK were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the corresponding targets were performed from Swiss Target Prediction. NSCLC-related targets were obtained from Therapeutic Target Database and Comparative Toxicogenomics Database. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were used to predict the potential signaling pathways involved in the treatment of advanced NSCLC with LK. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, A549 cell proliferation and migration assay were used to evaluate the antitumor activity of LK. Western blot was used to further verify the expression of key target proteins related to the predicted pathways.
resultsKaplan-Meier survival analysis showed that the overall survival of the CM group was longer than that of the non-CM group (36 months vs. 26 months), and COX regression analysis showed that LK treatment was an independent favorable prognostic factor (P=0.027). Next, 97 components and 86 potential targets were included in the network pharmacology, KEGG and GO analyses, and the results indicated that LK was associated with proliferation and apoptosis. Moreover, molecular docking revealed a good binding affinity between the key ingredients and targets. In vitro, A549 cell proliferation and migration assay showed that the biological inhibition effect was more obvious with the increase of LK concentration (P<0.05). And decreased expressions of nuclear factor κB1 (NF-κB1), epidermal growth factor receptor (EGFR) and AKT serine/threonine kinase 1 (AKT1) and increased expression of p53 (P<0.05) indicated the inhibitory effect of LK on NSCLC by Western blot.
conclusionLK inhibits NSCLC by inhibiting EGFR/phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, NFκB signaling pathway and inducing apoptosis, which provides evidence for the therapeutic mechanism of LK to increase overall survival in NSCLC patients.
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