细胞凋亡是由一系列基因控制并受复杂信号调节的生理性、主动性细胞死亡行为，在多细胞生物的发育过程和自稳平衡（homeostasis）的维持过程中都发挥必不可少的作用。人参皂苷Rh2(G-Rh2)是人参的微量成分，不依赖Bcl-2和Bcl-xL的方式诱导癌细胞凋亡。我们的前期研究表明G-Rh2在极短时间内同时启动线粒体细胞色素C介导的内源型细胞凋亡通路和膜死亡受体介导的外源型细胞凋亡通路。该化合物能很好地克服因细胞凋亡通路受损而导致的癌细胞抗凋亡作用。然而，其在细胞内作用靶点和如何同时启动两种主要细胞凋亡通路的机制尚不清楚。本项目将1） 确定G-Rh2在细胞内的作用靶点；2）阐明G-Rh2作用靶点至已知细胞凋亡启动信号之间的信号转导过程。本项目的研究将发现细胞凋亡线粒体通路和膜受体通路的新的起始点，同时为攻克因失去细胞凋亡的调控所导致的癌症等各种疑难性疾病，提供新的靶标和先导化合物。

Apoptosis, a physiological form of cell death, is controlled by a series of genes and complex signals. It plays a central role in the development and homeostasis of multicellular organisms. Ginsenoside Rh2(G-Rh2), a trace compound of Panax ginseng C. A. Meyer, has been shown to induce cancer cell apoptosis in a Bcl-2 and Bcl-xL independent menner. Our previous study demonstrated that G-Rh2 triggers both mitochondrial cytochrome c mediated caspase-9/-3 activation pathway and membrane death receptor-mediated caspase-8/-3 activation pathway. Therefore, this compound successfully overcomes drug resistance of cancer cells caused by disruption of apoptosis pathway. However, its cellular targets and the molecular mechanism by which G-Rh2 initiates the two main apoptosis pathway are largely unknown. The objective of this application is to identify the cellular targets for G-Rh2 and define the signal transduction pathways from the target of G-Rh2.to known apoptosis pathways. At the completion of this project, we expect to find a new initiation mechanism for these two main caspase activation cascades, and to provide a new targets and candidate for developing novel anticancer drugs.