Based on network pharmacology, using methods such as molecular docking and gene difference analysis, small molecule compounds for the treatment of lung adenocarcinoma and lung squamous cell carcinoma were screened in saussurea involucrata, and new therapeutic targets were discovered

Abstract

Purpose: Based on systemic pharmacology and network pharmacology, to evaluate the therapeutic effect of saussurea involucrata (SAIN) on lung adenocarcinoma and lung squamous cell carcinoma (LUAD&LUSC) through clinical sample genetic difference analysis and compound-target molecular docking, and discover new The target of prevention or treatment of LUAD&LUSC. Materials and methods: Using the TCM System Pharmacology Database (TCMSP) as the starting point for preliminary selection of ingredients and targets (OB≥30%, DL≥0.18, n=9), with the GDC database as the end point, using Cytoscape 3.8, TBtools 1.082, AutoDock 4.2.6, R 4.0.4, PyMol and other tools have conducted a preliminary screening of the ingredients and targets of SAIN. In order to further screen the effective ingredients and targets, we used clinical samples from LUAD and LUSC from TCGA and GEPIA to perform genetic difference analysis (n=6), and perform biological process (BP) analysis (FDR) on these targets. ≤0.05, n=6), KEGG pathway analysis (FDR≤0.05, n=6), protein interaction network (PPI) analysis (n=6) and compounds-targets-pathways network analysis (n=6), obtain biological processes, disease pathways and various compounds regulated by targets-the relationship between targets and pathways. Through the precise molecular docking of ingredients and targets, we further screened the targets of the effective ingredients of SAIN (affinity≤-7.0 kcal/mol, H-Bond dist≤3.0, n=6) and visualized the data, Then these targets were verified by using PSORTⅡ, CELLO and BUSCA databases for subcellular localization prediction (n=6). Finally, use the large amount of TCGA clinical data provided by Cbiportal for the prognostic survival analysis of LUAD and LUSC for the genes obtained through the screening. , And consult a large number of documents to verify the results.Results: After screening, comparing, analyzing and verifying a series of data, it is finally confirmed that there are three main active ingredients in SAIN. They are Quercetin, Luteolin and Kaempferol, which mainly act on 6 protein targets. The target mainly regulates 20 signal pathways including Pathways in cancer, Transcriptional misregulation in cancer, EGFR tyrosine kinase inhibitor resistance, Adherens junction, IL-17 signaling pathway, Melanoma, Non-small cell lung cancer and MicroRNAs in cancer. The preventive or therapeutic effects of LUSC. Conclusion: There are three active compounds of Q, L and K in SAIN, which play a role in the treatment and prevention of NSCLC by directly or indirectly regulating the expression of genes such as MMP1, MMP3 and EGFR.