基于内质网应激的β-榄香烯干预NSCLC细胞的自噬稳态平衡作用及机制研究

项目名称： 基于内质网应激的β-榄香烯干预NSCLC细胞的自噬稳态平衡作用及机制研究

项目编号： No.81503306

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 姜子瑜

作者单位： 南京中医药大学

项目金额： 18万元

中文摘要： 肺癌细胞的自噬稳态平衡是其存活的重要机制，而内质网应激（ERS）是自噬稳态平衡的强诱导因素。β-榄香烯是温郁金的主要萜烯类化合物，课题组前期研究发现它通过调控非小细胞肺癌（NSCLC）A549细胞ERS诱导自噬，但机制未明。我们提出“β-榄香烯抑制NSCLC细胞增殖与其干预、调控ERS介导自噬作用相关”的科学假说。拟采用透射电镜、Western blotting、RT-PCR、免疫组化、siRNA、GFP-LC3单荧光体系/mRFP-GFP-LC3双荧光体系、工具药物等技术研究β-榄香烯调控NSCLC细胞ERS和自噬特征变化，分析ERS、自噬稳态、细胞存活之间的关联，筛选相关靶标研究可能信号途径，揭示β-榄香烯调控NSCLC细胞自噬稳态平衡作用及其机制，为干预、治疗肺癌提供新的策略和靶点。本研究对深入理解β-榄香烯干预肺癌的作用机理和推动肺癌创新中药新药的研发具有重要理论价值和实际意义。

中文关键词： β-榄香烯；内质网应激；非小细胞肺癌；自噬稳态平衡

英文摘要： Autophagic homeostasis is an important mechanism for survival of lung cancer cells，and endoplasmic reticulum stress (ERS) is one of the potent factors for autophagic homeostasis. β-elemene is a major terpenoid compound of Chinese herbal medicine Curcuma wenyujin Y.H.Chen et C.Ling, with a potential anti-cancer activity. The pre-results of research group in this project showed that β-elemene could regulate ERS-mediated autophagy of non-small cell lung cancer (NSCLC) A549 cells, however, its underlying mechanism remains unknown. On the basis of our previous studies, we proposed a scientific hypothesis on “Inhibition of β-elemene on proliferation of NSCLC cells might be related closely with regulating ERS-mediated autophagy”. In this study, we intend to use transmission electron microscopy, Western blotting, RT-PCR, immunohistochemistry, siRNA, GFP-LC3 single fluorescence system/mRFP-GFP-LC3 double fluorescent systems, tool molecules and other technologies to study the regulation of β-elemene on ERS features and autophagic homeostasis changes of NSCLC cells; to analyze correlation of ERS, autophagy homeostasis, cell survival combined with mathematical statistics, and to screen related targets; to further research the possible signal pathway. This study ultimately reveals the effect and mechanism of β-elemene on autophagy of NSCLC cells, and provides a new strategy and new targets for the intervention and treatment of NSCLC. The project has an important theoretical and practical significance for the in-depth understanding of the intervention mechanism of β-elemene on NSCLC and promotes innovation and development of new drugs for NSCLC.

英文关键词： β-elemene;endoplasmic reticulum stress;NSCLC;autophagic homeostasis