本课题采用CE-MS深入分析“青蒿-鳖甲”药对配伍前后的化学图谱特征；将“青蒿-鳖甲”药对及其中的代表性成分（青蒿素衍生物等）作用于裸鼠移植瘤的动物实验和基因沉默构建质粒转染的细胞中探讨HIF1α-miR-124-P4HA1信号通路中HIF1α、miR-124、P4HA1 的基因和蛋白表达水平，检测细胞和肿瘤组织中MMP1和FLRT3的蛋白水平。同时采用CE-MS完成各组药物处理后的细胞胞内外代谢产物和裸鼠的血、尿、瘤组织的代谢组学分析；最后通过生物素标记技术完成青蒿素衍生物在该信号通路中的跟踪。通过动物、细胞、分子“三个水平”探讨这一新颖的信号通路中羟脯氨酸与“青蒿-鳖甲”药对以及青蒿素衍生物等代表性成分之间的相关性，进而阐明羟脯氨酸在“青蒿-鳖甲”药对抑制肝癌中的关键作用，为深化对疗效确切的传统中医药方剂的科学认知提供科学依据，为新的分子靶点的发现以及广泛的临床应用提供可能。

Artemisia apiacea-turtle shell drug pairs (ATD) were selected to be studied for their antitumor effect based on their significance revealing by literatures reviewing and clinical investigation. Individual and combined chromatography chemical features of the two medicines will be profiled through capillary electrophoresis mass spectrometry analysis. Representative active components of ATD (such as artemisinin and its derivatives) will be applied to tumor-burden nude mice and cells with HIF1a, miR-124 and P4HA1 genes silencing using siRNA tactic. The three corresponding gene expression and protein levels will also be evaluated to discuss the mechanism roles and biological significance of HIF1α-miR-124-P4HA1 (H124P)pathway in view of tumor suppression. Capillary electrophoresis-mass spectrometry will be employed to profile the metabolome difference of cells with or without treatment of using active components in ATD. Simultaneously, biofluids of serum and urine and tumor tissues from tumor burden mice will also subjected to metabolomic analysis individually. Finally intracellular artemisinin distribution will be traced through biotin labeling. At the levels of animals, cells and molecules, we want to explain the relationship among ATD, the derivatives of artemisinin and H124P pathway and the antitumor roles of hydroproline metabolism potentially regulated by ATD. The aim of the study is to help provide objective proof to support the scientific basis of Traditional Chinese Medicine prescription and to facilitate the new drug target discovery and utilization clinically.