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Exploring Beta-sitosterol’s Role in Breast Cancer Treatment via Integrated Network Pharmacological Analysis and in vitro Validation

作者:Jiaxing Yu, Shuqin Cheng, Zelin Ye, Ming Zhang, Xinlei Zhao · 发表于:Pharmacognosy Magazine · 年份:2024 · DOI:10.1177/09731296241294143 · 被引用次数:3 · 研究领域:Cholesterol and Lipid Metabolism、Computational Drug Discovery Methods、Estrogen and related hormone effects

Background Beta-sitosterol, a phytosterol similar to cholesterol, is found in various plants and is recognized for its potential anticancer properties; still, the mechanism of breast cancer (BC) remains elusive. Objectives This study investigates the potential targets of beta-sitosterol in BC using network pharmacological analysis and in vitro validation. Materials and Methods Targets of beta-sitosterol and BC were identified from online databases, including Swiss Target Prediction, SuperPred, GeneCards, and DisGeNET. Protein–protein interactions of common targets were analyzed using STRING version 11.0, and network construction and core target screening were performed with Cytoscape 3.8.0. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene ontology (GO) annotation were conducted using the ShinyGO web tool. Molecular docking analysis was done with AutoDock Vina and the in vitro validation, including cell viability, apoptosis, and gene expression analysis was done using MTT assay, acridine orange/ethidium bromide staining, and polymerase chain reaction (PCR), respectively. Results Sixty-eight common targets for beta-sitosterol and BC were identified from 209 beta-sitosterol targets and 1,350 BC-related genes. Five core targets (HIF1A, ESR1, STAT3, TNF, and MAPK3) were identified. GO analysis linked common targets to biological processes, cellular components, and molecular functions. KEGG pathway analysis showed enrichment in pathways such as ce...