酪氨酸激酶抑制剂（TKI）是非小细胞肺癌中目前应用最广的靶向药物，但其获得性耐药已成治疗难题。基于生物信息学分析和预实验发现：“枢纽基因”PRKCA可能在TKI耐药中起关键作用；长链非编码RNA-HCP5可能作为ceRNA通过吸附miR-186-5p调节PRKCA表达而影响肺癌TKI耐药；此外，中药黄栌提取物Fisetin可能逆转细胞耐药。因此，我们拟采用细胞和动物模型验证：HCP5/miR-186-5p/PRKCA轴活化导致EGFR下游的生存信号通路激活，可能是肺腺癌TKI耐药的重要机制，还可能是肺癌治疗的新靶点，Fisetin可能通过该机制逆转细胞耐药。本研究旨在探索肺腺癌的TKI耐药新机制，为肺癌TKI耐药治疗和新药研制提供新的思路及实验数据，对开发新的肺癌治疗策略具有重要的理论意义。

Tyrosine kinase inhibitor (TKI) is currently the most widely used target drug in non-small cell lung cancer, but its acquired drug resistance has become a serious problem. Based on bioinformatics analysis and preliminary experiments, PRKCA has been suggested to play a key role in TKI resistance. Long-chain non-coding RNA-HCP5 may act as ceRNA to regulate PRKCA expression by sponging miR-186-5p, which may affect TKI resistance of lung cancer. Furthermore, Fisetin, an extract of Quercus platyphylla, may reverse cell TKI resistance. Therefore, we aim to establish cell and animal models to verify that activation of the HCP5/miR-186-5p/PRKCA axis leads to activation of the downstream survival signaling pathway of EGFR, which may be an important mechanism of TKI resistance in lung adenocarcinoma and a new target for its treatment. Fisetin may reverse cell TKI resistance through this axis. This study can help explore new mechanisms of TKI resistance in lung adenocarcinoma, provide new ideas and experimental data for TKI resistance therapy and drug development, and develop new therapeutic strategies for lung adenocarcinoma.