NHC Key Laboratory of Control of Tropical Diseases, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan 571199, China.
School of stomatology, Hainan Medical university, Haikou, Hainan 571199, China.
Ecotoxicol Environ Saf. 2024 Oct 1;284:116866. doi: 10.1016/j.ecoenv.2024.116866. Epub 2024 Aug 22.
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.
本研究旨在阐明常见增塑剂（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））在乳腺癌发病机制中的潜在作用的分子机制。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的复杂相互作用。
我们采用网络毒理学和分子对接技术分析了增塑剂与乳腺癌中关键蛋白的相互作用。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。富集分析用于鉴定与这些基因相关的生物学途径。
富集分析突出了这些增塑剂靶向基因与腺癌发展相关途径的关联，表明增塑剂对激素依赖性和其他形式的癌症有广泛影响。随后使用 TCGA 乳腺癌数据库中的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著上调或下调，证实了它们在肿瘤生物学中的关键作用。此外，分子对接分析表明，包括 DEP、DMP 和 DOP 在内的增塑剂与关键蛋白（如 MAPK1、AKT1、SRC、ESR1 和 ALB）表现出特异性结合相互作用，这些蛋白在调节乳腺癌发病机制中至关重要。
该研究提供了证据表明，暴露于增塑剂可能通过与关键蛋白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，我们的研究结果突出了增塑剂的潜在风险。这些结果强调需要进行进一步的流行病学和临床研究，以充分了解增塑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。
