阐明通过网络毒理学和分子对接分析诱导乳腺癌的增塑剂机制
Elucidating the mechanism of plasticizers inducing breast cancer through network toxicology and molecular docking analysis
影响因子:6.10000
分区:环境科学与生态学2区 / 毒理学1区 环境科学2区
发表日期:2024 Oct 01
作者:
Na He, Jing Zhang, Mingyu Liu, Li Yin
摘要
这项研究的目的是阐明通常使用的增塑剂（包括邻苯二甲酸二乙酯（DEP），邻苯二甲酸二甲酯（DMP）（DMP）和邻苯二甲酸二链酰苯甲酸二甲酸二甲酯（DOP））的潜在贡献的分子机制。这项研究旨在强调这些环境化学物质与涉及肿瘤发生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来分析塑料与乳腺癌中涉及的塑料蛋白之间的相互作用。利用数据库（例如TCGA），我们对乳腺癌组织中选定的关键基因进行了表达分析，与正常对照组相比。进行了富集分析以识别与这些基因相关的生物学途径。富集分析强调了这些靶向增塑剂基因与腺癌发育不可或缺的途径的关联，这表明塑料化剂对激素依赖性和其他形式的癌症产生了广泛的影响。随后使用来自TCGA乳腺癌数据库数据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的显着上调或下调，证实了它们在肿瘤生物学中的关键作用。此外，分子对接分析表明，包括DEP，DMP和DOP在内的增塑剂表现出与关键蛋白（例如MAPK1，AKT1，SRC，ESR1和ALB）的特定结合相互作用，这对于乳腺癌致病的调节至关重要。通过采用网络药理学，蛋白质相互作用和分子对接，我们的发现突出了增塑剂带来的潜在风险。这些结果强调了进一步的流行病学和临床研究的必要性，以充分了解增塑剂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。
Abstract
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.