基于网络毒理学和分子对接的塑化剂毒性影响和胃癌机制的评估
Ning Tang1, Jingke Zhang1, Zhe Jiang2
1Liaoning University of Traditional Chinese Medicine Xinglin College, Shenyang, P. R. China.
Drug and chemical toxicology
|February 24, 2026
概括
像DBP和DEP这样的可塑剂可能会通过破坏关键细胞通路引发胃癌. 网络毒理学确定了与这种环境风险有关的特定基因和分子相互作用.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 塑化剂,如双甲 (DBP) 和二甲甲 (DEP),是常见的环境污染物.
- 它们在诱导胃癌的潜在作用和潜在的分子机制仍然不完全理解.
研究的目的:
- 通过网络毒理学研究DBP和DEP暴露引起的胃癌的分子机制.
- 为了确定潜在的分子点和途径,涉及到塑化剂诱导的毒性.
主要方法:
- 网络毒理学的方法是整合多个数据库 (PharmMapper,瑞士目标预测,基因卡,OMIM,药物银行,TTD).
- 确定了143个相关目标,并构建了一个网络图.
- 基因本体学 (GO) 和基因和基因组的京都百科全书 (KEGG) 路径丰富分析.
- 蛋白与蛋白相互作用 (PPI) 网络分析 (cytoHubba).
- 分子对接,以评估塑化剂与关键标的结合亲和力.
主要成果:
- 确定了143个潜在的分子标,其中10个中心基因包括AKT1,GRB2,EGFR,HRAS,JAK2,PIK3CG,PIK3CD,PIK3R1,PTPN11和SRC.
- 分析显示了诸如"癌症途径"",Ras信号途径"和"MAPK信号途径"等途径的参与.
- 分子对接证实了DBP/DEP与PIK3CG,PIK3CD,JAK2,HRAS和PTPN11之间强烈的结合亲和力.
结论:
- 塑化剂暴露,特别是DBP和DEP,可能会成为胃癌发展的环境触发因素.
- 网络毒理学为了解环境污染物的毒性提供了有价值的框架.
- 确定了分子目标和途径,为进一步的研究和干预提供了潜在的途径.
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