Research Paper Volume 14, Issue 14 pp 5812—5837
Elucidating the pharmacological mechanism by which Si-Wu-Tang induces cellular senescence in breast cancer via multilevel data integration
- 1 Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical University, Foshan 528000, PR China
- 2 Department of Emergency, Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical University, Foshan 528000, PR China
Received: April 19, 2022 Accepted: June 27, 2022 Published: July 19, 2022
https://doi.org/10.18632/aging.204185How to Cite
Copyright: © 2022 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Traditional Chinese medicine (TCM) is a promising strategy for effectively treating cancer by inducing cellular senescence with minimal side effects. Si-Wu-Tang (SWT) is a TCM composed of four herbs that is commonly used in China for the treatment of gynecological diseases; SWT can prevent breast cancer (BC), but the molecular mechanism by which SWT induces cellular senescence and its clinical application value remain unknown. We identified 335 differentially expressed genes (DEGs) in SWT-treated MCF-7 cells through Gene Expression Omnibus (GEO) dataset analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the enrichment of biological processes and key signaling pathways including cellular senescence, the cell cycle, the MAPK signaling pathway, and the p53 signaling pathway. Additionally, SWT induced BC cell senescence by upregulating the expression of 33 aging/senescence-induced genes (ASIGs). According to LASSO regression analysis, NDRG1, ERRFI1, SOCS1, IRS2, IGFBP4, and BIRC3 levels were associated with BC prognosis and were used to develop risk scores. ERRFI1, SOCS1, IRS2, IGFBP4, and BIRC3 were identified as protective factors (P < 0.05, HR < 1), while NDRG1 was identified as a risk factor (P < 0.05, HR > 1). Notably, patients with low risk scores had increased senescence-associated secretory phenotypes (SASPs) and immune cell infiltration. Overall, we systematically integrated biological databases and biocomputational methods to reveal the mechanisms by which SWT induces senescence in breast cancer and its clinical value.
Abbreviations
BC: breast cancer; SWT: Si-Wu-Tang; TCM: traditional Chinese medicine; DEGs: differentially expressed genes; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; ASIGs: aging/senescence-induced genes; SASP: senescence-associated secretory phenotypes; OS: overall survival; PPI: protein-protein interaction; ASI: aging/senescence-induced; ROC: receiver operating characteristic; AUC: areas under the curve; FDR: false discovery rate; LASSO: Least absolute shrinkage and selection operator; BP: biological process; CC: cytological component; MF: molecular function; GSEA: Gene Set Enrichment Analysis; H-AC: herb-active components; TILs: tumor-infiltrating lymphocytes; BRCA: breast invasive carcinoma; TIME: tumor immune microenvironment; TCMSP: Traditional Chinese Medicine System Pharmacology Database; OB: oral bioavailability; DL: drug-likeness; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; FPKM: fragments per kilobase million; TPM: transcripts per million.