Abstract
Purpose Network pharmacology and molecular docking were uesd to forecast the related effect targets and potential signal pathways of Rhubarb and Agastache rugosa in curing renal cancer. Methods Searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to screen the effective ingredients and targets of Rhubarb and Agastache rugosa, the differential genes related to renal cancer were obtained by searching GEO database. Construct the regulatory networks and protein-protein interaction(PPI) networks using Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed based on Metascape database, the gene set was analyzed by GSEA. The active components and core genes were molecular docked, and the core genes were analyzed for clinical correlation and immune infiltration. Finally, in order to verify the results of network pharmacological analysis, we performed cell experiments with 786-O cells and ACHN cells in vitro. Results The top six core genes, EGFR, HSP90AA1, MMP9, KDR, CA9, and LDHA, were identified by network pharmacological analysis; and Rhubarb and Agastache rugosa was predicted to play a role in the PI3K/Akt/mTOR pathway through central carbon metabolism in cancer. Cellular experiments showed that Rhubarb and Agastache rugosa restrained the proliferation of 786-O and ACHN cells, induced apoptosis, arrested the cell cycle, and reduced the colony forming ability of cells. qRT-PCR results showed that the expression of core targets of EGFR, HSP90AA1, MMP9, KDR, CA9, and LDHA were significantly down-regulated. Western blot results showed that the protein expression levels of EGFR, p-PI3K, PI3K, p-Akt/Akt, and p-mTOR/mTOR were significantly down-regulated. Discuss The core targets in the effective components of Rhubarb and Agastache rugosa may be to inhibit the development and proliferation of renal carcinoma cells through the PI3K/Akt/mTOR pathways.