Abstract

Background: Shenmai Injection (SMI) can effectively benefit the prognoses of patients with advanced Colo Rectal Carcinoma (CRC). However, the mechanism by which SMI treats CRC patients remains obscure.

Methods: The primary active ingredients of SMI and corresponding targets were collected via TCMSP and ETCM databases. The CRC-related genes were gathered by Malacards database. The Protein-Protein Interaction (PPI) analysis of target genes and CRC-related genes was conducted using STRING database. Random Walk with Restart (RWR) analysis of PPI network was conducted with drug-targeted CRC-related genes as seed genes, and the top 50 genes in affinity coefficient were selected to construct the network diagram of drug-active ingredient-gene interactions. GO and KEGG enrichment analyses were conducted on the top 50 genes in affinity coefficient. Finally, the interaction between protein and critical small molecule compound was simulated by using RSCB PDB database, Pub Chem database and molecular docking tool Swiss Dock.

Results: PPI network and RWR analysis manifested the interaction between the genes targeted by active ingredients of SMI and CRC-related genes. The top 50 genes in affinity coefficient were conspicuously enriched in the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance and several life processes associated with transmembrane transport, as demonstrated by the outcomes of GO and KEGG enrichment analyses. As exhibited by the outcomes of molecular docking, a stable docking model was formed between the target protein MAPK3 closely related to CRC and the critical small molecule compound adenosine in SMI.

Conclusion: This study elucidated the critical small molecule compound of SMI and its target for CRC treatment on the foundation of network pharmacology, RWR method and molecular docking, and preliminarily analyzed the molecular mechanism of SMI treating CRC, providing a reference direction for subsequent cell assays and a scientific basis for the treatment of CRC with SMI.