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

Shuyu Liu,Xiaohong Hu,Ruiqi Jin,Jiarui Wu,Yifei Geng,Wenqian Yang,Xiaotian Fan

doi:10.1155/2020/2758640

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.

Highlights

Modern medicine has made great progress in cancer research, breast cancer (BC) remains an important health issue
It is shown that compound Kushen injection (CKI), as a Traditional Chinese medicine (TCM) compound preparation, has a good synergistic antitumor effect by inhibiting tumor cell proliferation and inducing differentiation
Active Ingredients and Potential Targets of CKI. ere is a systematic and comprehensive search of published literature on the active compounds of CKI in CNKI, Wanfang, VIP database, and PubMed. e SMILES (Simplified Molecular Linear Input Specification) structures of the screened compounds were obtained using the PubChem database, and putative targets were collected from the Search Tool for Interacting Chemicals (STITCH, http://stitch.embl.de/), SuperPred, and Swiss Target Prediction databases and TCM Pharmacology Database and Analysis Platform (TCMSP, http://tcmspw.com/tcmsp.php) [20,21,22,23]

Summary

Introduction

Modern medicine has made great progress in cancer research, breast cancer (BC) remains an important health issue. BC is the most common cancer affecting women’s health around the world, and its morbidity and mortality are expected to increase dramatically in the few years [1]. Studies have shown that radiotherapy and chemotherapy can increase the risk of myelodysplastic disorder and acute myeloid leukemia in BC patients, which means more pain for patients with poor body function and poor tolerability [2]. It is shown that compound Kushen injection (CKI), as a TCM compound preparation, has a good synergistic antitumor effect by inhibiting tumor cell proliferation and inducing differentiation. It has been widely used in clinical practice in China [8]. CKI is prepared from a series of refined processes including percolation, boiling, and alcohol absorption of Sophora flavescens and Smilax glabra, which is able to clear heat and promote diuresis, cool blood and detoxify, resolve stagnation, as well as relieve pain [9]

Methods

Discussion

Conclusion