NLRP3炎症小体介导炎性微环境对舌癌干细胞形成的调控作用及机制研究

炎性微环境对肿瘤干细胞的形成具有重要作用，NLRP3炎症小体在炎性微环境中扮演着重要角色，但其对肿瘤干细胞的作用尚不清楚。结合前期的研究，我们提出如下假说：“NLRP3炎症小体介导的炎性微环境对舌癌干细胞的形成具有重要调控作用”。研究拟从以下几个方面开展：①检测舌癌组织中NLRP3炎症小体、炎性微环境及肿瘤干细胞相关因子的表达及其相关性；②将舌癌细胞与巨噬细胞、MDSCs共培养，添加NLRP3相关外源性重组因子或中和抗体，检测其对舌癌干细胞的影响；③通过过表达和沉默NLRP3基因，分析其对舌癌干细胞的影响，检测IKK/NF-κB、IL-6/STAT3信号通路及其下游分子的改变；④探索NLRP3炎症小体作为分子靶标在舌癌治疗中的可行性。通过对NLRP3炎症小体介导的炎性微环境在舌癌干细胞形成调控机制中的研究，可为舌癌的早期预防及靶向治疗提供新思路。

NLRP3 inflammasome plays an important role in the inflammatory microenvironment which contributes to the formation of cancer stem cells, but its effects on cancer stem cells remains unclear. Based on our previous studies, we propose the hypothesis: “NLRP3 inflammasome mediated inflammatory microenvironment plays an important role in the formation of tongue cancer stem cells”. This project developes as following: ①analyzing the expression and correlation of NLRP3 inflammasome, inflammatory microenvironment and cancer stem cell related factors; ②co-culturing tongue cancer cells with macrophages or MDSCs, while add NLRP3 related exogenous recombinant factors or neutralizing antibodies, detecting their effects on the formation of cancer stem cells; ③to analyze the effects of overexpression or knockdown NLRP3 on cancer stem cells formation, check the changes of IKK/NF-κB, IL-6/STAT3 signal and their targets; ④experimental study of targeting NLRP3 inflammasome for tongue cancer treatment. This study investigates the roles of NLRR3 inflammasome on the formation of cancer stem cells, which provides new insight for the the prevention and target treatment of tongue cancer.