乙酰胆碱通过间接激活雄激素受体调控肝癌细胞的运动和凋亡

本实验室最近首次发现：肝癌细胞存在自分泌/邻分泌非神经来源的乙酰胆碱系统，它们与肝癌细胞的增殖及药敏性相关。我们前期研究发现在肝癌细胞株，乙酰胆碱上调雄激素受体（androgen receptor，AR）的表达并增强其转录活性。本项目拟在人肝癌细胞株、裸鼠及人肝癌组织探讨乙酰胆碱（Acetylecholine，Ach）是否通过非雄激素依赖途径激活AR，进而对肝癌细胞运动和凋亡产生影响。本项目首次在脏器水平探索肝癌发生发展的神经递质-激素-肿瘤的系统调控模式，并对其参与肝癌发生发展的作用机制进行探讨，从而为肝癌致病机制提供新的理论依据，为肝癌的诊断和治疗提供新的靶标。

We have recently for the first time demonstrated that the autocrine acetylcholine (Ach) system exists and modulates tumor progression by affecting cell proliferation and chemosensitivity in hepatocellular carcinoma (HCC). In our preliminary study, we found that Ach enhanced androgen receptor (AR) expression and its transcriptional activity. In this proposal, we would like to investigate the effects of Ach on HCC cell motility and apoptosis and further explore whether these effects are dependent on Ach-induced AR transactivation. This project would be the first study demonstrating the cross-talk between neural/non-neural neurotransmitters and endocrine in HCC development, which could uncover new mechanisms of HCC development and provide new strategy for the management of HCC.