新颖的millpuline A型双黄酮基于调控lncRNA-XIST表达的肺癌化学预防作用研究

非小细胞肺癌（NSCLC）约占所有肺癌的80%，其发病率高、生存率低。因此发现能特异性逆转NSCLC关键致病基因异常表达的新型肺癌化学预防剂，对于NSCLC的有效防治具有重要的意义。前期研究中发现lncRNA-XIST的异常表达在NSCLS的发病过程中起到关键作用，随后应用高表达lncRNA-XIST的细胞模型筛选了系列天然药物，首次从壮药玉郎伞中发现了一类结构新颖的双黄酮骨架——millpuline A型由四元碳环聚合而成的双黄酮，且这一新骨架表现出了显著下调lncRNA-XIST异常表达的活性。基于此，本项目旨在利用LC-MS/NMR快速发现技术和化学合成方法构建millpuline A型双黄酮物质库，探讨其生合成途径，系统评价其肺癌化学预防活性和通过下调lncRNA-XIST水平进而调控肺癌预防关键基因的作用机制，并首次构建这类新骨架体外下调lncRNA-XIST异常表达的构效关系。

About 80% patients of lung cancer were diagnosed as nonsmall cell lung cancer (NSCLC). NSCLC is characterized by a high incidence and poor survival rate and difficult to be detected early. Therefore, it’s critical for the prevention and therapy of NSCLC to find out effect chemopreventive agents targeted on the specific pathogenic genes of NSCLC. In our previous research, it was found that the abnormal expression of lncRNA-XIST should be related to the development of NSCLC. Then, targeted screening was carried out in natural herbals using the cell model high expressed with lncRNA-XIST. As a result, a novel skeleton of biflavone, millpuline A, with a four member of carbon cycle in the structure, was identified from Yulangsan which is a traditional Zhuang nationality medicine. Based on the previous result, we propose to rich the structure of the novel skeleton by means of phytochemical research and synthesis method. Furthermore, the biosynthesis pathway will be discussed. And its lung cancer chemopreventive effect will be assayed in vitro and in vivo. Finally, the possible mechanism should be explored on the regulation of lncRNA-XIST and the related downstream genes. Moreover, the structure and activity relationship of the novel natural products on down-regulation of lncRNA-XIST could be constructed for the first time.