细胞自噬是肿瘤耐药的重要原因，诱导细胞自噬性死亡和/或凋亡是逆转肿瘤耐药的有效手段，PI3K-Akt-mTOR信号通路是细胞凋亡、自噬与肿瘤耐药调控的汇聚点。中医认为正气虚损是肺癌顺铂耐药发生的主要原因，前期研究发现培土生金法分别通过抑制PI3K-Akt信号通路、调控耐药相关基因mTOR表达等方式有效干预肺癌顺铂耐药。本项目以PI3K-Akt-mTOR为切入点，以顺铂耐药肺癌原位移植瘤动物模型和A549/DDP细胞为研究对象，运用小动物活体成像系统、RNAi、透射电镜、免疫印迹等技术，分别在组织、细胞、蛋白及基因水平上，观察培土生金法对肺癌顺铂耐药及自噬信号通路相关蛋白及其底物的调控，阐明培土生金法干预PI3K-Akt-mTOR信号通路诱导细胞自噬性死亡逆转NSCLC顺铂耐药的机制，为寻找中西医结合治疗肺癌的有效干预靶点提供实验依据，同时为丰富肺癌耐药病机与治法理论提供新的思路与方法。

Autophagy is an important reason for the tumor drug resistance, so inducing cell autophagic death and/or apoptosis is an effective method to relieve tumor drug resistance. PI3K-Akt-mTOR signaling pathway is the focal point which affects apoptosis, autophagy and tumor drug resistance. Traditional Chinese Medicine (TCM) holds that “insufficiency of healthy-Qi” is the principal reason of cisplatin resistance of lung cancer. Early research has shown that the method of strengthening the lung by way of reinforcing the spleen can effectively intervene in cisplatin resistance of non-small cell lung cancer (NSCLC) through inhibiting PI3K-Akt signaling pathway and intervening mTOR expression. Regarding the PI3K-Akt-mTOR signaling pathway as the entry point, with the model of cisplatin resistance of lung orthotopic transplantation tumor models and A549/DDP cells as the study object, by techniques of animal In-Vivo Imaging System, RNAi, transmission electron microscopy and immunoblotting, the project study that the method of strengthening the lung by way of reinforcing the spleen effects intervening cisplatin-resistant cells of NSCLC on inner relation and the feedback mechanism of gene and protein expression of signal related proteins and substrate. So the subject explores the mechanism of the method of strengthening the lung by way of reinforcing the spleen intervening cisplatin resistance of NSCLC by inducing cell autophagic death on PI3K-Akt-mTOR signaling intervening, which further proves PI3K-Akt-mTOR singal transduction regulation is feasible as a new target which improves cisplatin resistance of NSCLC. And it will provide the referable experimental method and theoretical basis for filtering Chinese medicine to improve cisplatin resistance.