暴露于内分泌破坏者DEHP通过增加BMI1表达和癌症干细胞的特性来促进胰腺癌细胞的进展和放射疗法抗性
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
影响因子:6.10000
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
摘要
大多数被诊断出患有胰腺癌的患者最初处于晚期阶段，放射疗法耐药性会影响治疗的有效性。这项研究旨在研究内分泌干扰物Di-（2-乙基己基）邻苯二甲酸酯（DEHP）对胰腺癌细胞的各种生物学行为和放疗敏感性及其潜在机制的影响。我们的发现表明，暴露于DEHP会促进各种癌细胞的扩散，包括肺，乳腺癌，胰腺和肝脏的癌细胞以时间和浓度依赖性方式的增殖。此外，DEHP暴露可能会影响体内胰腺癌细胞的几种生物学行为。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，增强肿瘤性，升高癌症干细胞（CSC）的比例（CSC）以及上调CSC标记的表达水平，例如CD133和BMI1。 DEHP暴露还可以增加辐射电阻，可以通过下调BMI1表达来逆转。总而言之，我们的研究表明，DEHP暴露会导致胰腺癌的进展和放射疗法抗性，并且该机制可能与BMI1表达的上调有关，这导致CSCS性质的增加。
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.