Division of Cardiology , Chang Gung Memorial Hospital, Kaohsiung Medical Center , Kaohsiung 833 , Taiwan.
Graduate Institute of Clinical Medicine , Kaohsiung Medical University , Number 100, Tzyou First Road , Kaohsiung 807 , Taiwan.
J Agric Food Chem. 2018 Sep 19;66(37):9635-9644. doi: 10.1021/acs.jafc.8b03558. Epub 2018 Sep 6.
Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer that is widely used in many consumer products and medical devices. Humans can be exposed to DEHP through ingestion, inhalation, or dermal absorption. Previous studies on DEHP have focused on its role as an endocrine-disrupting chemical leading to endocrine-related diseases. However, the correlation between DEHP exposure and the progression of colorectal cancer (CRC) is largely unknown. The aim of this study was to investigate the effects of mono(2-ethylhexyl) phthalate (MEHP), an active metabolite of DEHP, on the progression of CRC. Our results showed that treatment with MEHP enriched the population of cancer-stem-cell (CSC)-like cells and upregulated IL-8 expression by inducing the AKT-β-catenin-TCF4 signaling pathway. Blocking β-catenin-TCF4-mediated IL-8 expression reversed the MEHP-induced migration and enrichment of CSC-like cells. Consistent with the in vitro data, DEHP treatment increased the levels of nuclear β-catenin, polyp formation, and invasive adenocarcinoma in a mouse model. Our results suggest that MEHP facilitates the progression of CRC through AKT-β-catenin signaling.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种常见的增塑剂，广泛应用于许多消费品和医疗器械中。人类可以通过摄入、吸入或皮肤吸收接触 DEHP。先前关于 DEHP 的研究主要集中在它作为一种内分泌干扰化学物质导致与内分泌相关的疾病方面。然而，DEHP 暴露与结直肠癌（CRC）进展之间的相关性在很大程度上尚不清楚。本研究旨在探讨邻苯二甲酸单（2-乙基己基）酯（MEHP），DEHP 的一种活性代谢物，对 CRC 进展的影响。我们的研究结果表明，MEHP 处理富集了具有癌症干细胞（CSC）样特征的细胞，并通过诱导 AKT-β-catenin-TCF4 信号通路而上调了 IL-8 的表达。阻断β-catenin-TCF4 介导的 IL-8 表达逆转了 MEHP 诱导的 CSC 样细胞的迁移和富集。与体外数据一致，DEHP 处理增加了核 β-catenin、息肉形成和侵袭性腺癌的水平在小鼠模型中。我们的研究结果表明，MEHP 通过 AKT-β-catenin 信号促进 CRC 的进展。
