基于SIRT3的线粒体生物学效应：黄酮类化合物千层纸素调控肿瘤细胞能量代谢的抗肿瘤机制研究

靶向的抑制促进肿瘤细胞生长的能量代谢反应是当前科学家热点研究的癌症治疗策略之一。SIRT3是一种定位于线粒体的脱乙酰酶，通过作用于线粒体中的能量代谢相关酶，严格调控着细胞的糖酵解、TCA和呼吸链等代谢过程以及线粒体功能。千层纸素是一种在体内外均具有较强抗肿瘤活性的天然黄酮类化合物，其抗肿瘤作用与线粒体功能调节、凋亡诱导相关。基于SITR3对线粒体的生物学效应，探讨千层纸素通过如何作用SIRT3而影响肿瘤细胞的能量代谢。本课题重点围绕SIRT3、HIF-1α、p53和HKⅡ，研究千层纸素影响糖酵解发挥其抑制肿瘤生长或诱导凋亡的作用；同时，探索性研究千层纸素通过SIRT3对肿瘤细胞的线粒体呼吸链、TAC的影响，寻找到可能的有效的作用靶点，为日后的深入研究奠定基础。

The altered metabolism of tumors has been considered as a target for anticancer therapy. SIRT3 is a mitochondrial deacetylase, which tightly regulates the cellular metabolic processes such as glycolysis, TCA and the respiratory chain as well as the mitochondrial function via deacetylating the mitochondrial enzymes. Oroxylin A is a natural flavonoid with strong anti-tumor activity both in vitro and in vivo, which can modulate the mitochondrial functions and induce apoptosis in cancer cells. Based on the mitochondrial biological effects mediated by SITR3, we study how oroxylin A regulates energy metabolism through SIRT3 in cancer cells. This project mainly focuses on the anticancer mechanism of oroxylin A by modulating glycolysis concerning SIRT3, HIF-1α，p53 and HK-II, resulting in the growth inhibition or apoptosis induction of cancer cells ultimately. Besides, we would explore the influences of oroxylin A on the mitochondrial respiratory chain and TAC by regulating SIRT3 in cancer, aiming to find the possible effectors or targets for further studies.