和厚朴酚通过靶向抑制TrxR1上调ROS发挥抗小儿睾丸卵黄囊瘤的活性及机制研究

项目名称： 和厚朴酚通过靶向抑制TrxR1上调ROS发挥抗小儿睾丸卵黄囊瘤的活性及机制研究

项目编号： No.81673643

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 陈肖鸣

作者单位： 温州医科大学

项目金额： 25万元

中文摘要： 厚朴是我国中医药典籍广泛记载的一味药材，和厚朴酚 (HNK)是其主要活性成分之一，具有多种药理活性，包括抗肿瘤作用，但其抗肿瘤机制和直接分子靶点尚不清楚。我们前期发现HNK在小儿睾丸卵黄囊瘤细胞中可以激活氧化应激而诱导肿瘤细胞凋亡，且发现HNK可以直接结合并抑制小儿卵黄囊瘤中高表达的胞内氧化还原系统的重要调节酶TrxR1。因此，我们推测HNK可能是通过靶向抑制TrxR1，激活ROS而发挥其抗肿瘤的作用，TrxR1可能成为小儿睾丸卵黄囊瘤的重要治疗靶点。本项目拟在分子和细胞层面明确TrxR1是HNK的直接靶点，阐明HNK通过TrxR1和ROS在小儿睾丸卵黄囊瘤细胞中诱导细胞凋亡的信号机制，验证HNK体内抗肿瘤活性及TrxR1的作用。本项目将明确HNK的抗肿瘤药理分子机制和直接靶点，为小儿睾丸卵黄囊瘤的防治提供新药物。

中文关键词： 和厚朴酚；硫氧还蛋白还原酶1；活性氧；小儿睾丸卵黄囊瘤；天然产物

英文摘要： Magnolia bark is one of chinese traditional medicines widely used from ancient time. Honokiol (HNK) is one of the main bioactive constituents of Magnolia bark and it exhibit broad pharmacological properties, including anti-tumor activity. However, the role of HNK in pediatric testicle yolk sac tumor and its definite target remain unclear. A key enzyme named TrxR1 has recently been reported regulating ROS levels markedly. Moreover, our preliminary studies showed that HNK could elevate levels of ROS generation observably as well as bind to TrxR1 and inhibit its activity in order to induce apoptosis in yolk sac tumor cells consequently. Therefore, we predicted that HNK kill testicle yolk sac tumor cells probably through ROS overproduction by targeting the TrxR1. . Firstly, our project is proposed to clarify the TrxR1 as the exact target site of HNK. Secondly,We will reveal the molecular mechanism and signal pathway of apoptosis inducement of HNK through TrxR1 and ROS on testicle yolk sac tumor cells. Thirdly, we plan to design series of in vivo experiments to conform the anticancer activity of HNK and to illuminate the affect of the TrxR1 in pediatric testicle yolk sac tumor cells. In conclusion，investigation of the exact target and molecular anti- pediatric testicle yolk sac tumor mechanism of HNK will provide new insights into its prevention and treatment.

英文关键词： Honokiol;TrxR1;ROS;Pediatric testicle yolk sac tumor ;Natural product