原发性肝癌是一种严重威胁人类健康的恶性肿瘤。尽管已有不少合成药物用于治疗肝癌，但多数药物导致明显的毒副作用。近年来，传统中药治疗肝癌疗效显著并引起广泛关注。我们最近研究发现石蒜有显著的抗肝癌活性，然而目前对其抗肝癌的整体作用机制和化学物质基础的研究仍十分薄弱。本项目拟发展基于功能蛋白质组学及亲和超滤质谱技术的新方法用于中药石蒜抗肝癌的作用机理和物质基础的研究。首先，利用植物化学方法结合体外肝癌细胞活性评价，获得石蒜抗肝癌的有效组分；其次，应用定量蛋白质组学方法，分析肝癌造模前后及石蒜有效组分干预肝癌动物模型前后表达差异的蛋白，鉴定肝癌发病相关蛋白及石蒜抗肝癌的关键目标蛋白；在此基础上，采用超滤质谱技术，以前述的目标蛋白为靶点，筛选并鉴定石蒜抗肝癌的活性化合物。最后，通过揭示化合物作用的蛋白靶点，构建石蒜抗肝癌活性化合物的靶点蛋白网络，阐明中药石蒜抗肝癌的化学物质基础和作用机制。

Hepatocarcinoma is one of the most frequent malignant tumors. Although numerous synthetic medicines have been approved in clinical use for the treatment of hepatocarcinoma, most of them may lead to serious side effects. While the traditional Chinese medicines (TCMs) have significant efficacy for the treatment of hepatocarcinoma, and thus attracted considerable interest nowadays. Our recent studies provide evidences that Lycoris radiata showed good activity against hepatocarcinoma. However, its overall anti-tumor mechanisms of action and the responsible compounds in Lycoris radiata have remained elusive, and poorly studied due to its complex multi-component , multi-target feature and lack of effective strategies to date. In this context, we propose to develop and apply a new strategy for exploring the overall anti-hepatocarcinoma mechanisms of action and active compounds in Lycoris radiata based on functional proteomics and ultra-filtration LC-MS. Firstly, we prepare different effective fractions in Lycoris radiata and evaluate their inhibitory activity against Hep G2 cells. Secondly, we select the hepatocarcinoma animal models to investigate the effects of Lycoris radiata on overall proteomic changes using deuterium isobaric amine reactive tag (DiART) labeling based quantitative proteomics and subsequent bioinformatics analysis, in this way we could identify and predict multiple molecular targets related to hepatocarcinogenesis or affected by the treatment with Lycoris radiata. we then further develop ultra-filtration liquid chromatography-mass spectrometry assay to screen for the active compounds in Lycoris radiata using the protein targets verified in the aforementioned proteomic study. Finally, the interaction networks between the active compounds and their respective targets could be constructed, thus the mechanisms of action and active compounds in Lycoris radiata for the treatment of hepatocarcinoma could be elucidated.