肺腺癌靶向药物EGFR-TKI已取得了历史性突破，但治疗后会出现复发或转移，导致肿瘤细胞产生耐药性。不断探索靶向药物耐药机制，克服耐药的发生是迫切需要的。前期研究中成功建立EGFR-TKI耐药细胞株后，进行基因芯片分析，发现在EGFR-TKI耐药细胞中GSK-3β高表达，通过Westernblot证实活化的GSK-3β也高表达。通过siRNA敲除GSK-3β后发现下游靶基因NF-κB相关基因明显低表达，表明肺癌EGFR-TKI可能通过GSK-3β/NF-κB信号轴产生耐药，但其具体机制仍不清楚。基于前期研究结合循环肿瘤细胞、耐药细胞株、组织蜡块、动物实验的结果观察GSK-3β和NF-κB相关基因的分子生物学特性，阐明GSK-3β/NF-κB信号轴对肺腺癌转移和EGFR-TKI耐药的作用机制，进一步探讨EGFR-TKI耐药后可否利用GSK-3β和NF-κB抑制剂恢复药物敏感性。

EGFR-TKI is a breaking history target therapy in lung adenocarcinoma, but patients occur recurrence and metastasis, also resistance to EGFR-TKI after 6-10 months. Many research tried to explore the mechanism of EGFR-TKI resistance, and it was very urgent to patients. In previous studies, we established the EGFR-TKI resistant cell lines, and performed microarray analysis. We found that GSK3β was overexpressed in resistant cells, and confirmed with western blot. Using siRNA to knock down GSK-3β can induce low expressions of downstream NF-κB related target genes. Based on previous study, we aimed to illuminate the mechanism of metastasis and resistance of EGFR-TKI in lung adenocarcinoma by co-active of GSK3β and NF-κB pathway,using Circulating tumor cells, resistant cells, tissue paraffin blocks and mouse. Finally, we tried to observe whether GSK-3β and NF-κB inhibitors can make EGFR-resistant lung cancer to regain drug-sensitivity.