与正常细胞相比，癌细胞的代谢网络发生了重编程——更多地依赖有氧酵解途径获取能量，这既是癌变的中心环节，又是耐药的重要原因。PI3K-Akt-mTOR信号通路是肿瘤细胞糖代谢重编程与耐药调控的汇聚点。中医认为正气虚损是肺癌顺铂耐药的主要原因，前期研究发现培土生金法可通过干预PI3K-Akt-mTOR信号通路诱导细胞凋亡与自噬性死亡有效逆转肺癌顺铂耐药。本项目继续以PI3K-Akt-mTOR为切入点，以顺铂耐药、有氧酵解程度高的A549/DDP细胞为模式细胞，运用小动物PET-CT、RNAi、real-time PCR、免疫印迹等技术，利用体内、外实验观察培土生金法对肿瘤耐药及糖代谢重编程信号通路中相关蛋白及其底物的调控，阐明培土生金法干预PI3K-Akt-mTOR信号通路逆转肿瘤细胞糖代谢重编程增加NSCLC顺铂敏感性的机制，为肺癌的治疗提供干预靶点、为丰富肺癌耐药病机与治法理论提供新思路。

Compared to the normal cells that depend on oxidative phosphorylation metabolic pathways responsible for generating ATP, cancer cells increase glycolysis for their reprogramming of metabolic networks. The carbohydrate metabolic reprogramming of cancer cells is not only the central of tumorigenesis, but also an important reason of tumor drug resistance. And PI3K-Akt-mTOR signaling pathway is the focal point which affects carbohydrate metabolic reprogramming 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 inducing apoptosis and autophage. Regarding the PI3K-Akt-mTOR signaling pathway as the entry point, with the model of A549/DDP cells higher in cisplatin resistance and carbohydrate metabolic reprogramming as the study object, by techniques of animal PET-CT, RNAi, real-time PCR 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 reversal carbohydrate metabolic reprogramming 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.