“促炎症消退”介质RvE1抗乳腺癌作用机制研究

Chronic inflammation is closely related to the development of breast cancer. Coordinated program of resolution initiates in the first time few hours after an inflammatory response begins, named” programed resolution” of inflammation. When the tumor precipitating factors leading to inflammation persists, SPM is relatively low. Emerging evidence showed that RvE1 is able to prevent excessive inflammation, and our previous results indicated that RvE1 can inhibit proliferation of breast cancer in spontaneous breast cancer mouse models. Thus we make a hypothesis that RvE1 plays anti-cancer effect in breast cancer via regulating "chronic inflammatory tumor microenvironment". Further studies are going to focus on RvE1's potential of adjusting the balance of Thl/Th2 RvE1, Th17/Treg axis, tumor-associated macrophages M2-type polarization and TNF-α-NF-ΚB/snail epithelial-mesenchymal transformation. The aim of this project is to explore the pathogenesis of breast cancer in the aspect of regulating "chronic inflammatory tumor microenvironment", which may lead to a novel therapeutic strategy for breast cancer.

慢性炎症与乳腺癌发生发展关系密切。炎症反应在启动同时就已经规划了炎症消退——炎症“程序性消退”，而当肿瘤导致炎症促发因素持续存在时，炎症消退介质（SPM）则相对不足。 新近发现的内源性SPM中，消退素RvE1具有纳克级促炎症消退的作用，我们的前期实验结果表明RvE1受体表达于多种乳腺体癌细胞系，RvE1可以抑制自发乳腺癌小鼠模型中肿瘤的生长。基于此，本课题拟通过补充外源性RvE1和Chemerin多肽/U75302阻断RvE1受体而对乳腺癌进行干预，明确RvE1直接作用以及通过调节“慢性炎性肿瘤微环境”而起到抗乳腺癌效应，进而研究RvE1如何调节乳腺癌中Thl/Th2 平衡、Th17/Treg 轴、巨噬细胞的M2极化，如何作用于TNF-α-NF-κB/snail信号通路下调上皮间质转化。拟从“慢性炎性肿瘤微环境”角度深入认识乳腺癌的发病机制，明确“促进炎症消退”是治疗乳腺癌合理有效的新策略

慢性炎症与乳腺癌发生发展关系密切。炎症反应在启动同时就已经规划了炎症消退——炎症“程序性消退”，而当肿瘤导致炎症促发因素持续存在时，炎症消退介质（SPM）则相对不足。放射治疗导致炎症介质增高，消退素RvE1可降低炎症介质，直接降低放疗导致的ITGA6，从而增加放射治疗敏感性。进一步研究表明，消退素RvE1影响ITGA6，通过PI3K/AKT, MEK/ERK通路发挥作用。本课题从炎症与乳腺癌治疗疗效的新视角阐述了一新的机制。