本研究的目的是阐明常用增塑剂（包括邻苯二甲酸二乙酯 (DEP)、邻苯二甲酸二甲酯 (DMP) 和邻苯二甲酸二辛酯 (DOP)）对乳腺癌发病机制的潜在影响的分子机制。本研究旨在强调这些环境化学物质与肿瘤发生中涉及的关键分子途径之间复杂的相互作用。我们采用网络毒理学和分子对接技术来分析增塑剂与乳腺癌中涉及的关键蛋白质之间的相互作用。利用 TCGA 等数据库，我们对乳腺癌组织中选定的关键基因与正常对照进行了表达分析。进行富集分析以确定与这些基因相关的生物途径。富集分析强调了这些塑化剂靶向基因与腺癌发展不可或缺的途径的关联，表明塑化剂对激素依赖性癌症和其他形式的癌症具有广泛的影响。随后使用 TCGA 乳腺癌数据库数据进行的表达分析表明，与正常对照相比，这些基因在乳腺癌组织中显着上调或下调，证实了它们在肿瘤生物学中的关键作用。此外，分子对接分析显示，包括DEP、DMP和DOP在内的增塑剂与MAPK1、AKT1、SRC、ESR1和ALB等关键蛋白表现出特异性结合相互作用，这些蛋白在乳腺癌发病机制的调节中至关重要。研究提供的证据表明，接触增塑剂可能通过与关键蛋白质和信号通路的相互作用影响乳腺癌的发病机制。通过采用网络药理学、蛋白质相互作用和分子对接，我们的研究结果强调了增塑剂带来的潜在风险。这些结果强调需要进一步的流行病学和临床研究，以充分了解塑化剂暴露对乳腺癌风险的影响，从而为未来的预防和治疗策略提供信息。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

The objective of this study was to elucidate the molecular mechanisms underlying the potential contribution of commonly utilized plasticizers, including Diethyl phthalate (DEP), Dimethyl phthalate (DMP), and Dioctyl phthalate (DOP), to the pathogenesis of breast cancer. This study aimed to highlight the complex interactions between these environmental chemicals and key molecular pathways implicated in tumorigenesis.We employed network toxicology and molecular docking techniques to analyze the interactions between plasticizers and key proteins implicated in breast cancer. Utilizing databases such as the TCGA, we performed an expression analysis of selected key genes in breast cancer tissue compared to normal controls. Enrichment analysis was conducted to identify the biological pathways associated with these genes.Enrichment analysis highlighted the association of these plasticizer-targeted genes with pathways integral to adenocarcinoma development, suggesting a broad impact of plasticizers on hormone-dependent and other forms of cancers. Subsequent expression analysis using data from the TCGA breast cancer database indicated significant upregulation or downregulation of these genes in breast cancer tissues compared to normal controls, confirming their pivotal roles in tumor biology. Furthermore, the molecular docking analysis revealed that plasticizers, including DEP, DMP, and DOP, exhibit specific binding interactions with key proteins such as MAPK1, AKT1, SRC, ESR1, and ALB, which are crucial in the regulation of breast cancer pathogenesis.The study provides evidence that exposure to plasticizers may influence breast cancer pathogenesis through interactions with critical proteins and signaling pathways. By employing network pharmacology, protein interactions, and molecular docking, our findings highlight the potential risks posed by plasticizers. These results underscore the need for further epidemiological and clinical research to fully understand the implications of plasticizer exposure on breast cancer risk, thus informing future preventive and therapeutic strategies.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.