IL-1β可通过多种机制促进肿瘤细胞迁移。肿瘤相关巨噬细胞（TAM）可通过活化NLRP3炎症小体表达分泌IL-1β，是肿瘤免疫微环境IL-1β的重要来源。本课题旨在探索通过精密调控TAM NLRP3炎症小体/IL-1β轴抑制非小细胞肺癌转移的可能性。兼备肿瘤细胞杀伤作用与肿瘤免疫微环境调节作用的化合物值得深入研究。铁死亡是一种新近被报道的程序性细胞死亡方式。Erastin可诱导Ras突变的癌细胞发生铁死亡，但其对肿瘤免疫微环境的影响尚不明确。本课题前期结果表明，Erastin可显著下调小鼠Lewis肺癌TAM IL-1β的表达水平。因此，我们提出假说：铁死亡诱导剂Erastin可通过调控TAM NLRP3炎症小体/IL-1β轴抑制非小细胞肺癌转移。本课题将揭示Erastin调控NLRP3炎症小体活化的分子机制，及其对非小细胞肺癌转移的影响。本课题有可能为非小细胞肺癌的治疗提供潜在的新策略。

IL-1β has been reported to promote tumor cell migration in non-small-cell lung cancer (NSCLC) via various mechanisms. Tumor-associated macrophages (TAMs) are important source of IL-1β in tumor immune microenvironment. TAMs are known to express and release IL-1β via NLRP3 inflammasome activation. In this study, we aimed to explore the possibility of inhibiting NSCLC metastasis by tightly regulating NLRP3 inflammasome/IL-1β axis in TAMs. Chemicals having both tumor cell cytotoxic effects and immunoregulatory effects deserve further investigation. Ferroptosis is a recently described form of programmed cell death. Erastin has been widely reported to induce ferroptosis in cancer cells with oncogenic Ras mutations. However, the effects of erastin on tumor immune microenvironment remain elusive. In this study, we found that erastin significantly downregulated IL-1β expression in TAMs isolated from Lewis lung cancer mice. Hence, we hypothesized that the ferroptosis inducer erastin would inhibit NSCLC metastasis via regulating NLRP3 inflammasome/IL-1β axis in TAMs. We would demonstrate the molecular mechanisms underlying the regulatory effects of erastin on NLRP3 inflammasome activation, and would explore the effects of erastin on NSCLC metastasis. And we'll have chance to provide a potential strategy for NSCLC treatment.