胶质瘤是中枢神经系统最常见的肿瘤之一，占脑肿瘤的近80%，死亡率和发病率极高。表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）作为EGFR靶向治疗各类实体瘤；然而，神经胶质瘤的有效治疗仍然有限。奥西替尼是一种不可逆的口服第三代 TKI，针对 T790M 突变，该突变会导致癌细胞获得耐药性。奥希替尼可有效治疗 EGFR 突变，且对野生型 EGFR 活性的影响极小。黑色素瘤中缺失 2 (AIM2) 在神经胶质瘤细胞中高表达，促进促癌细胞因子的成熟并促进神经胶质瘤的进展。然而，肿瘤细胞分泌促癌细胞因子被认为是包括奥希替尼在内的EGFR-TKI的耐药机制。这些细胞因子的高水平还表明无进展生存期 (PFS) 较短。由于AIM2调节促癌细胞因子的分泌，我们认为抑制AIM2可能有助于EGFR-TKIs的治疗效果。我们首先建立了细胞中AIM2的抑制和过度表达。采用细胞计数试剂盒8（CCK-8）法计算细胞存活率，流式细胞仪测定细胞凋亡率。采用定量聚合酶链反应（qPCR）检测炎症相关基因的表达，采用酶联免疫吸附测定（ELISA）测定炎症相关因子的浓度。采用蛋白质印迹法检测Wnt/b-catenin和EGFR/Ras/Mitogen激活蛋白激酶激酶1（MEK）信号通路成分的表达。我们发现抑制AIM2放大了奥希替尼上调炎症基因表达的作用这些基因的分泌，增加细胞凋亡。此外，我们还发现AIM2可以增强奥希替尼降低Wnt/b-catenin和EGFR/Ras/MEK信号通路表达的作用，从而抑制细胞增殖，发挥抗肿瘤作用。使用体内实验也观察到了这些效应。AIM2 为神经胶质瘤的治疗提供了潜在的治疗靶点。

Glioma is one of the most commonly tumours which occurs in the central nervous system and accounts for nearly 80% of brain tumours, with a significantly high mortality and morbidity. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as EGFR targeted therapy in various types of solid tumours; however, effective treatment for glioma is still limited. Osimertinib is an irreversible, oral third-generation TKI that targets the mutation at T790M, which causes cancer cells to acquire resistance to drugs. Osimertinib could be effective in the treatment of EGFR mutations with minimal effects on the activity of wild-type EGFR. Absent in melanoma 2 (AIM2) is highly expressed in glioma cells, promoting the maturation of pro-cancer cytokines and contributing to progression of glioma. However, the secretion of pro-cancer cytokines of tumour cells has been regarded as the resistance mechanism to EGFR-TKIs, including osimertinib. A high level of these cytokines also indicates a shorter progression-free survival (PFS). As AIM2 regulates the secretion of pro-cancer cytokines, we thought inhibition of AIM2 may contribute to the therapeutic effect of EGFR-TKIs.We first established AIM2 inhibition and overexpression in cells. Then, the viability rate of cells was calculated by cell counting kit-8 (CCK-8) method, and apoptotic ratio of cells were measured by flow cytometry. The expression of inflammatory-related genes was detected using quantitative polymerase chain reaction (qPCR), concentrations of inflammatory-related factors were measured using enzyme-linked immunosorbent assay (ELISA). The expression of Wnt/b-catenin and EGFR/Ras/Mitogen-activated protein kinase kinase 1 (MEK) signalling pathway components was detected using western blotting.We found that inhibition of AIM2 enlarged the effect of osimertinib on the upregulation of inflammatory gene expression and secretion of these genes, increasing apoptosis. In addition, we also found that AIM2 could enhance the effect of osimertinib on reducing the expression of the Wnt/b-catenin and EGFR/Ras/MEK signalling pathways, resulting in the inhibition of cellular proliferation, and exerting an anti-tumour effect. These effects were also observed using in vivo experiments.AIM2 presents a potential therapeutic target in treatment of glioma.