培土生金法干预PI3K/Akt信号通路抑制上皮-间质转化在NSCLC顺铂耐药中的研究

项目名称： 培土生金法干预PI3K/Akt信号通路抑制上皮-间质转化在NSCLC顺铂耐药中的研究

项目编号： No.81473569

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘春英

作者单位： 辽宁中医药大学

项目金额： 72万元

中文摘要： 上皮-间质转化（EMT）是肿瘤耐药的重要原因，PI3K/Akt信号通路是影响EMT诸多因素激发胞内信号的汇聚点。中医学认为正气虚损是肺癌顺铂耐药的主要原因，前期研究表明培土生金法可有效干预肺癌顺铂耐药。本项目借助信号转导网络研究策略，以EMT与肿瘤多药耐药（MDR）的共同调控点PI3K/Akt信号通路为切入点，以肺癌顺铂耐药动物模型和A549/DDP细胞为研究对象，运用分子生物学、血清药理学等技术，研究培土生金法对肺癌顺铂耐药细胞信号相关蛋白及其底物的基因及蛋白表达的内在联系和反馈机制，探讨培土生金法干预PI3K/Akt信号通路抑制EMT在NSCLC顺铂耐药中的作用机制，进一步证明PI3K/Akt信号转导调控作为改善肺癌顺铂耐药新靶点的可行性，为筛选具有选择性干预PI3K/Akt信号转导而改善肺癌耐药的中医药提供可靠实验手段和理论依据，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。

中文关键词： 非小细胞肺癌；上皮-间质转化；PI3K/Akt；培土生金法

英文摘要： Epithelial-Mesenchymal Transition (EMT) is the important reason for the tumor drug resistance. PI3K/Akt signaling pathway is the focal point which affects EMT and stimulates intracellular signal. 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 lung cancer. With the help of research strategy of signal transduction network, with the PI3K/Akt signaling pathway which is collectively regulated by EMT and Multidrug resistance (MDR) as the entry point, with the model of cisplatin resistance of lung cancer and A549/DDP cells as the study object, by techniques of molecular biology, serum pharmacology, etc, the project studies that the method of strengthening the lung by way of reinforcing the spleen effects cisplatin-resistant cells of lung cancer 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 non-small cell lung cancer induced by PI3K/Akt signaling pathway inhibiting epithelial-interstitial transformation, further proves PI3K/Akt signal transduction regulation is feasible as a new target which improves cisplatin resistance of lung cancer, and provides the referable experimental method and theoretical basis for filtering Chinese medicine which improves cisplatin resistance of lung cancer through selectively intervening PI3K/Akt signaling and a new idea or theory for the pathogenesis and therapy of lung cancer resistance.

英文关键词： non-small cell lung cancer;epithelial-mesenchymal transition;PI3K/Akt;method of strengthening the lung by way of reinforcing the spleen