Network Pharmacology Based Elucidation of Molecular Mechanisms of Laoke Formula for Treatment of Advanced Non-Small Cell Lung Cancer  

作　　者：FENG Yu-yu LIU Jin-feng XUE Yang LIU Dan WU Xiong-zhi 

机构地区：[1]Department of Nursing,Tangshan Vocational and Technical College,Tangshan,Hebei Province 063000,China [2]School of Chinese Materia Medica,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China [3]Department of Oncology,Tianjin Medical University General Hospital,Tianjin 300020,China [4]Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin's Clinical Research Center for China,Tianjin 300060,China [5]Tianjin Nankai Hospital,Tianjin Medical University,Tianjin 300100,China

出　　处：《Chinese Journal of Integrative Medicine》2024年第11期984-992,共9页中国结合医学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China(Nos.82174103 and 81473441)。

摘　　要：Objective: To 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. Methods: Kaplan-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. Results: Kaplan-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 pr

关 键 词：LaoKe Formula non-small cell lung cancer network pharmacology ANTI-TUMOR Chinese medicine 

分 类 号：R285[医药卫生—中药学]