大多数被诊断患有胰腺癌的患者最初都处于晚期，放疗抵抗会影响治疗的效果。本研究旨在探讨内分泌干扰物邻苯二甲酸二(2-乙基己基)酯(DEHP)对胰腺癌细胞多种生物学行为和放疗敏感性的影响及其潜在机制。我们的研究结果表明，接触 DEHP 会以时间和浓度依赖性方式促进各种癌细胞的增殖，包括来自肺癌、乳腺癌、胰腺和肝脏的癌细胞。此外，DEHP 暴露可能影响胰腺癌细胞的体内和体外多种生物学行为。这些作用包括减少细胞凋亡、导致 G0/G1 期停滞、增加迁移能力、增强致瘤性、提高癌症干细胞 (CSC) 的比例以及上调 CSC 标志物（如 CD133 和 BMI1）的表达水平。 DEHP 暴露还会增加辐射抵抗力，这可以通过下调 BMI1 表达来逆转。综上所述，我们的研究表明，DEHP暴露可导致胰腺癌进展和放疗抵抗，其机制可能与BMI1表达上调，从而导致CSCs特性增加有关。版权所有©2024 The Authors。由爱思唯尔公司出版。保留所有权利。

Most patients diagnosed with pancreatic cancer are initially at an advanced stage, and radiotherapy resistance impact the effectiveness of treatment. This study aims to investigate the effects of endocrine disruptor Di-(2-ethylhexyl) phthalate (DEHP) on various biological behaviors and the radiotherapy sensitivity of pancreatic cancer cells, as well as its potential mechanisms. Our findings indicate that exposure to DEHP promotes the proliferation of various cancer cells, including those from the lung, breast, pancreas, and liver, in a time- and concentration-dependent manner. Furthermore, DEHP exposure could influence several biological behaviors of pancreatic cancer cells in vivo and vitro. These effects include reducing cell apoptosis, causing G0/G1 phase arrest, increasing migration capacity, enhancing tumorigenicity, elevating the proportion of cancer stem cells (CSCs), and upregulating expression levels of CSCs markers such as CD133 and BMI1. DEHP exposure can also increase radiation resistance, which can be reversed by downregulating BMI1 expression. In summary our research suggests that DEHP exposure can lead to pancreatic cancer progression and radiotherapy resistance, and the mechanism may be related to the upregulation of BMI1 expression, which leads to the increase of CSCs properties.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.