TCDD-induced antagonism of MEHP-mediated migration and invasion partly involves aryl hydrocarbon receptor in MCF7 breast cancer cells
TCDD-induced antagonism of MEHP-mediated migration and invasion partly involves aryl hydrocarbon receptor in MCF7 breast cancer cells
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TCDD 诱导的 MEHP 介导的迁移和侵袭的拮抗部分涉及 MCF7 乳腺癌细胞中的芳烃受体
DOI：
10.1016/j.jhazmat.2020.122869
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发表时间：
2020
影响因子：
13.6
通讯作者：
Tang Nai-jun
中科院分区：
文献类型：
--
作者：
Shan Anqi;Leng Ling;Li Jing;Luo Xiu-mei;Fan Ya-jiao;Yang Qiaoyun;Xie Qun-hui;Chen Yang-sheng;Ni Chun-sheng;Guo Li-ming;Tang Hua;Chen Xi;Tang Nai-jun
有证据表明，AhR（芳烃受体）的激活可以促进癌细胞转移。然而，对于混合暴露于内分泌干扰化学物质（EDC）的研究非常有限，特别是在人类乳腺癌中。因此，利用 MCF7 人乳腺癌细胞，我们研究了同时暴露于 MEHP（邻苯二甲酸单 2-乙基己酯）和 TCDD（2,3,7,8-四氯二苯并-对二恶英）对细胞迁移和侵袭的影响，以及 AhR 和 MMP/slug 通路的作用。我们的数据表明MEHP或TCDD可以诱导MCF7细胞的迁移和侵袭，并且这种促进部分依赖于AhR。我们还观察到 MEHP 拮抗 TCDD 以减少 AhR 介导的 CYP1A1 表达。随后，我们发现 MEHP 将 AhR 招募到二恶英反应元件 (DRE) 序列，并减少 CYP1A1 基因中 TCDD 诱导的 AhR-DRE 结合。总体而言，MEHP 是一种潜在的 AHR 激动剂，能够减少 TCDD 诱导的 AhR-DRE 在 CYP1A1 基因中的结合。共暴露的拮抗作用导致MCF7细胞的上皮-间质转化（EMT）受到抑制。我们的研究为 EDC 暴露及其在 EMT 中相互作用的潜在机制提供了新的证据。
Evidence has shown that the activation of AhR (aryl hydrocarbon receptor) can promote cancer cell metastasis. However, limited studies have been carried out on mixed exposure to endocrine-disrupting chemicals (EDCs), especially in human breast cancer. Therefore, using MCF7 human breast cancer cells, we investigated the effects of coexposure to MEHP (mono 2-ethylhexyl phthalate) and TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) on cell migration and invasion, as well as the roles of AhR and the MMP/slug pathway. Our data suggest that MEHP or TCDD can induce migration and invasion in MCF7 cells, and the promotion is partly AhR dependent. We also observed that MEHP antagonized TCDD to reduce AhR-mediated CYP1A1 expression. Subsequently, we revealed that MEHP recruited AhR to dioxin response element (DRE) sequences and decreased TCDD-induced AhR-DRE binding in CYP1A1 genes. Overall, MEHP is a potential AHR agonist, capable of decreasing TCDD-induced AhR-DRE binding in CYP1A1 genes. The antagonizing effect of coexposure led to the inhibition of the epithelial–mesenchymal transition (EMT) in MCF7 cells. Our study provides new evidence for the potential mechanisms involved in EDCs exposure and their interactions in EMT.