OBJECTIVE  To explore the anti-tumor mechanism of Jianpi Jiedu Decoction (JPJDD) based on network pharmacology and molecular docking.

  METHODS  TCMSP, TCMID and ETCM databases were used to predict the active ingredients and the targets of JPJDD, and GeneCards database was used to search tumor related targets and match the targets above. The common targets were imported into Cytoscape 3.7.2 to construct the PPI network and select the key targets by network topology analysis. GO enrichment analysis and KEGG pathway enrichment analysis were performed by R 3.6.3 software. Finally the Autodock 2.4 was used for molecular docking to predict the binding degree of the active ingredients to target genes. In addition, the key targets were verified by cell experiments.

  RESULTS  24 kinds of active ingredients and 86 tumor related targets were identified, including the key targets of PTGS2, HSP90AA1 and PRSS1, which were obtained by PPI network topology analysis. The molecular docking showed that all of the key targets had good binding activity with quercetin and kaempferol. GO enrichment analysis and KEGG pathway enrichment analysis suggested that JPJDD may play the role of anti-tumor through PI3K/Akt signal pathway and MAPK signal pathway. The results showed that JPJDD inhibited both the protein and mRNA expressions of PTGS2 and p38MAPK, but after silencing PTGS2 gene, the expression of downstream gene p38MAPK and the effect on colorectal cancer cells metastasis had no obvious response to JPJDD.

  CONCLUSION  JPJDD can inhibit the metastasis of colorectal cancer via PTGS2 mediated p38MAPK signaling pathway.