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.

Cell Cycle Arrest, An Important Mechanism of Action of Compound Kushen Injection, Prevents Colorectal Cancer: Network Pharmacology Analysis and Experimental Validation

“…2C). By integrating the findings of other research groups [17][18][19][20] and our present findings, we found that different cancers have many common CKI target pathways (such as HIF1, PI3K-Akt, ErbB, FoxO, and p53; Supplementary Table S5). Although there may be some overlap, the hub protein targets were quite different.…”

“…Compound Kushen injection was shown to play an anti-cancer role through multiple components, targets, and pathways. These anti-cancer mechanisms of action of CKI have demonstrated its anti-pan-cancer activities and specificity for some cancer types 16,[17][18][19][20] . For pan-cancers, He et al constructed a pharmacological network that was composed of 33 active components, 113 protein targets (including IL6, EGFR, CASP3, VEGFA, MYC, and ESR1), and a list of the top 20 signaling pathways (including the PI3K/AKT signaling pathway, p53 signaling pathway, apoptosis, proteoglycans in cancer, and pathways in cancer).…”

“…In recent years, the application of network pharmacology, RNA-Seq technology, and bioinformatics has become a good research tool for screening bioactive ingredients with anti-cancer properties and predicting target genes and related signaling pathways. The application of in vitro cells and in vivo animal models has also provided robust technical support for verifying the biological effects of CKI [16][17][18][19][20][21][22][23][24][25][26][27] .…”

“…These authors speculated that the potential molecular mechanism of action of CKI's anti-pan-cancer actions involves promotion of the p53and PI3K/Akt-mediated apoptosis of tumor cells 16 . For individual cancers, Zhou et al constructed a pharmacological "active ingredient-protein target-signaling pathway" network for gastric cancer, esophageal cancer, lung cancer, and breast cancer [17][18][19][20] . Zhou et al reported that CKI has a therapeutic effect on gastric cancer by synergistically regulating some biological pathways, such as the cell cycle, pathways in cancer, the PI3K-AKT signaling pathway, the mTOR signaling pathway, and the FoxO signaling pathway.…”

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“…Ganoderma lucidum from Ganoderma suppresses the proliferation and migration of breast cancer by inhibiting Wnt/β-catenin signaling (Zhang, 2017), while puerarin from Radix puerariae inhibits cell migration, invasion, and adhesion of LPS-induced BC by blocking NF-κB and Erk pathways . In addition to these herbal components, many formulas and proprietary Chinese medicines are widely used in the treatment of BC, such as compound kushen injection (CKI) (Liu et al, 2020), Shugan Jianpi decoction (Jingyuan et al, 2021), and Fangjihuangqi decoction (Guo et al, 2020). Based on these formulas and proprietary Chinese medicines, CKI is a commonly used antitumor treatment in clinical practice.…”