肺癌是目前病死率最高的常见恶性肿瘤。以化疗为主的综合治疗仍是晚期肺癌的主要治疗手段。肺癌细胞对化疗药物产生耐药，常常导致化疗失败。前期研究结果发现Cullin7（CUL7）与非小细胞肺癌(non-small cell lung cancer, NSCLC)发生、发展密切相关。而且，CUL7在多西他赛耐药的NSCLC细胞表达显著增高。为研究NSCLC多西他赛耐药机制和分子靶向治疗，本项目拟深入研究CUL7和抑制剂MLN4924在NSCLC多西他赛耐药中的作用及分子作用机制。研究确定CUL7是否通过上皮-间质转化（EMT）或3M复合体（FBXW8-CUL7-OBSL1- CCDC8）-CUL9-survivin通路等机制介导参与NSCLC细胞多西他赛耐药形成。研究结果将有助于阐明肺癌多西他赛耐药的分子机制，为肺癌的临床个体化用药或逆转耐药性的产生，以及肺癌的分子靶向治疗等提供关键的理论依据。

At present, Lung cancer is one of the most frequently diagnosed types of malignant tumor and a leading cause of mortality worldwide. Systemic chemotherapy is still an important treatment option for advanced lung cancer. However, drug resistance acquired by lung cancer cells usually leads to treatment failure. Our previous study showed that Cullin 7（CUL7）plays a critical role in the development and progression of non-small cell lung cancer (NSCLC). Furthermore, we found that the expression of CUL7 was significantly increased in the docetaxel-resistant NSCLC cells. To understand the underlying molecular mechanisms of docetaxel resistance in NSCLC and to identify molecular targets for therapy, this project aims to investigate the function of CUL7 and the inhibitor(MLN4924) in the docetaxel-resistant NSCLC cells. To determine whether CUL7 involved in docetaxel resistance of NSCLC by regulating epithelial - mesenchymal transition（EMT）or 3M complex（FBXW8-CUL7-OBSL1-CCDC8）-CUL9-survivin pathway. Our results will not only help to elucidate the underlying molecular mechanisms of docetaxel resistance in lung cancer, but also provide theoretical evidences for clinical personalized medicine, reversal of drug resistance or molecular targeted therapy in lung cancer.