PCBs暴露对乳腺癌细胞内铁代谢紊乱的调控机制以及所诱导的肿瘤学效应研究

The environmental pollution and healthy problems caused by PCBs have attracted great attention. Although the impact of PCBs exposure on cancers, including breast cancer, has been indentified, the molecular mechanisms of PCBs on breast cancer still remains elusive. The applicant's previous studies demonstrated that PCBs exposure induced iron overload in cancer cells and animals, and iron overload had.a significant role in the development of breast cancer. These results provide a new perspective and ideas for investigating the mechanisms of PCBs exposure on breast cancer. However, many details remain unclear. Thus, we are planning to perform the following studies: 1) the effects on the kinetics of iron metabolism, subcellular distribution and iron-related cell activities in breast cancer cells upon PCBs exposure. 2) the regulation and the mechanisms of iron-related gene expression under PCBs treatment. 3) the oncologic effects of PCBs exposure through dysregulating iron metabolism. The results and conclusions of this project would be helpful for the understanding on the molecular mechanisms of PCBs exposure on breast cancer, and lay foundations for the safety of the regional ecological environment, pollution prevention and effective management of PCBs in the futhure.

多氯联苯（Polychorinated biphenyls，PCBs）所引发的环境污染和健康问题一直是人们关注的焦点之一。目前，PCBs暴露对乳腺癌等高发性肿瘤的影响越来越明确，然而，整体上仍停留在“相关性”的认识水平上，对PCBs促乳腺癌的分子机理仍不清楚。本申请者的前期工作证实，PCBs暴露能够引起肿瘤细胞和动物体内的铁负荷，而铁负荷对乳腺癌具有显著的促进作用，这为研究PCBs的促乳腺癌机制提供了新的视角和思路，但很多细节仍不清楚。因此，我们将开展以下工作：1）PCBs暴露对肿瘤细胞内铁代谢的动力学特征、亚细胞分布和铁代谢相关细胞活动的调节；2）PCBs暴露对铁代谢基因的影响及作用机理；3）PCBs暴露造成的铁代谢紊乱所诱导的肿瘤学效应。本课题的研究成果将有助于深入理解PCBs暴露促乳腺癌的分子机制，同时为保证区域生态环境安全、有效预防和治理PCBs的污染问题奠定一定的基础。

多氯联苯（Polychorinated biphenyls，PCBs）所引发的环境污染和健康问题一直是人们关注的焦点之一。目前，PCBs暴露对乳腺癌等高发性肿瘤的影响越来越明确，然而，整体上仍停留在“相关性”的认识水平上，对PCBs促乳腺癌的分子机理仍不清楚。我们的工作证实：1）PCBs暴露能够引起肿瘤细胞和动物体内的铁负荷，而铁负荷对乳腺癌具有显著的促进作用，并且我们对机制进行了深入的探究；2）PCBs低浓度对乳腺癌细胞的活力和早期凋亡没有显著影响，但是能显著增加乳腺癌细胞的体外迁移能力；3）PCBs处理能显著影响铁代谢相关基因的表达；4）通过细胞实验以及动物实验我们证实HO-1参与了PCBs对乳腺癌转移的调控；5）拓展研究了多氯联苯对卵巢癌肿瘤干细胞特性的作用。本课题的研究成果将有助于深入理解PCBs暴露促乳腺癌转移的分子机制， 同时为保证区域生态环境安全、有效预防和治理PCBs的污染问题奠定一定的基础。