暴露于内分泌干扰物DEHP通过上调BMI1表达及癌症干细胞特性促进胰腺癌细胞的进展及放疗耐药性
Exposure to endocrine disruptor DEHP promotes the progression and radiotherapy resistance of pancreatic cancer cells by increasing BMI1 expression and properties of cancer stem cells
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影响因子:6.1
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 Sep 15
作者:
Min-Cong Wang, Bao-Feng Wang, Hong-Tao Ren, Yuan-Qing Huang, Jing-Chen, Ji-Yuan Pan, Hong-Bing Ma
DOI:
10.1016/j.ecoenv.2024.116970
摘要
大多数胰腺癌患者在诊断时处于晚期，放疗耐药性影响治疗效果。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及其放疗敏感性的影响及其潜在机制。我们的研究结果显示，暴露于DEHP促使多种癌细胞（包括肺、乳腺、胰腺和肝脏来源的细胞）在时间和浓度依赖性下增殖。此外，DEHP暴露可影响胰腺癌细胞的多种生物学行为，包括减少细胞凋亡、引起G0/G1期阻滞、增强迁移能力、提高肿瘤形成能力、增加癌症干细胞（CSC）比例，并上调CSC标志物如CD133和BMI1的表达水平。DEHP暴露还可以增强辐射抗性，而下调BMI1表达则可逆转此效应。综上所述，我们的研究表明，DEHP暴露可促进胰腺癌的进展和放疗耐药，其机制可能与BMI1表达上调有关，从而增加CSC的特性。
Abstract
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.