结直肠癌（Colorectal Cancer，CRC）发病率逐年上升，易转移且死亡率高，目前尚无有效治疗药物。傣药白钩藤具有清热解毒、消肿止痛之功效。现代药理学研究表明白钩藤具有潜在抗癌活性，但其药效物质基础及作用机制尚不明确。课题前期研究发现：（1）白钩藤中的钩藤碱具有调节CRC细胞葡萄糖代谢、诱导自噬、抑制增殖和转移活性；（2）PDK1与细胞葡萄糖代谢密切相关、与CRC患者的不良预后密切相关；（3）钩藤碱具有潜在靶向抑制PDK1、调控AMPK相关信号通路作用。基于此，本课题拟对白钩藤中生物碱类成分进行系统化学成分分离，筛选抗CRC活性目标化合物，阐明其抗CRC作用机制，验证“傣药白钩藤中生物碱类基于PDK1介导的代谢途径发挥抗CRC作用”科学假说，为傣药白钩藤的临床拓展应用提供理论依据，为作用于PDK1的新型抗CRC分子靶向药物研发提供理论基础。

Colorectal cancer (CRC) is a common cancer with increasing incidence, high aggressiveness and high mortality rates. There is no effective therapeutic drug until now. Dai medicine Uncaria sessilifructus Roxb. possesses qingrejiedu, xiaozhongzhitong effects. Modern pharmacological studies have shown that Uncaria sessilifructus Roxb. has potential anti-tumor activity, but its material basis and molecular mechanism remain unclear. Our previous research had identified that: (1) Rhynchophylline (Rhy) isolated from Uncaria sessilifructus Roxb. shows effects of cellular glucose metabolism regulation, cell proliferation and metastasis inhibition, autophagy promotion on CRC cells; (2) PDK1 correlates with cellular glucose metabolism, PDK1 correlates with poor prognosis of CRC patients; (3) Rhy potentially targets PDK1, mediates AMPK related signaling. Based on this, the research intends to separate alkaloids from Uncaria sessilifructus Roxb., screen the target compounds with higher anti-CRC activity and investigate their molecular mechanisms of anti-CRC effects in vitro and in vivo. The research will clarify anticancer molecular mechanism of alkaloids from Dai medicine Uncaria sessilifructus Roxb. on CRC based on PDK1 mediated-metabolic pathway. It may provide theoretical guidance for the expanding clinical application of Uncaria sessilifructus Roxb., and provide theoretical basis for the development of novel anti-CRC drugs targeting PDK1 mediated-metabolic pathway.