A Bioinformatics Research on Novel Mechanism of Compound Kushen Injection for Treating Breast Cancer by Network Pharmacology and Molecular Docking Verification

Abstract

Compound Kushen injection (CKI) has been extensively used in treating breast cancer (BC). However, the molecular mechanism remains unclear. In this study, 16 active compounds of CKI were obtained from 3 articles for target prediction. Then, a compound-predicted target network and a compound-BC target network were conducted by Cytoscape 3.6.1. The gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the DAVID database. The binding energy between the key targets of CKI and the active compounds was studied by molecular docking. As a result, 16 active compounds of CKI were identified, corresponding to 285 putative targets. The key targets of CKI for BC are HSD11B1, DPP4, MMP9, CDK1, MMP2, PTGS2, and CA14. The function enrichment analysis obtained 13 GO entries and 6 KEGG pathways, including bladder cancer, cancer pathways, chemical carcinogenesis, estrogen signaling pathway, TNF signaling pathway, and leukocyte transendothelial migration. The result of molecular docking indicated that DPP4 had strong binding activity with matrine, alicyclic protein, and sophoridine, and MMP9 had strong binding activity with adenine and sophoridine. In conclusion, the therapeutic effect of CKI on BC is based on the overall pharmacological effect formed by the combined effects of multiple components, multiple targets, and multiple pathways. This study provides a theoretical basis for further experimental research in the future.

Figure 1

Compound-target network. Notes: the blue squares represent active compounds of CKI, and the pink octagons represent the targets of these compounds.

Figure 2

Compound-BC target network. Notes: the blue diamonds represent active compounds of CKI, and the red circles represent the common targets.

Figure 3

GO functional enrichment analysis of key targets.

Figure 4

KEGG pathway enrichment analysis of key targets.

Figure 5

Illustration of crucial biological progress caused by key targets and known therapeutic targets for CKI.

Figure 6

Compound-target-pathway network. Notes: The pink diamond refers to CKI. The green triangles represent active compounds in CKI. The orange, red, and yellow circles represent putative targets of CKI. Among them, the red circles represent the common targets of CKI and BC, and the yellow circles represent key targets of CKI for the treatment of BC. The purple hexagons represent the main pathways of key targets.

Figure 7

Result of molecular docking. Notes: (a) lamprolobine acts on DPP4; (b) sophoridine acts on DPP4; (c) adenine acts on MMP9; (d) sophoridine acts on MMP9.