肝内胆管细胞癌恶性程度高，预后差，已有治疗药物疗效差，因此寻找新的治疗药物和作用靶点具有重要意义。我们前期研究发现中药蟾酥的有效单体蟾毒灵能抑制肝内胆管癌细胞增殖并促进其凋亡，通过蛋白质组和基因组芯片检测发现蟾毒灵能直接结合CaMKKβ蛋白，且基因CaMKIV的表达与CaMKKβ的表达呈正相关。结合已有文献报道，我们初步证实蟾毒灵可影响下游mTOR/S6K信号通路。由此可假设：蟾毒灵通过直接抑制CaMKKβ的活性抑制CaMKIV进而影响下游mTOR/S6K信号通路发挥其抗肿瘤作用。本课题拟从体外、体内角度研究蟾毒灵调控CaMKKβ/CaMKIV轴影响mTOR/S6K信号通路发挥其抗肿瘤机制，此研究成果将解释蟾毒灵在肝内胆管癌中发挥作用的具体机制，为肝内胆管细胞癌的有效治疗提供新药物和新靶点。

The prognosis of intrahepatic cholangiocarcinoma is dismal. Thus, exploration and identification of new drugs and targets are of vital importance in practice. Our previous studies have found that venenum Bufonis, a potent monomer of Chinese toad, inhibited the proliferation and promoted the apoptosis of intrahepatic cholangiocarcinoma cells. By detecting the proteome and genomic microarrays, bufalin could directly bind to CaMKKβ protein, and the gene expression of CaMKIV was positively correlated to CaMKKβ. Combined with relevant aticle reports, we preliminary confirmed that bufalin can affect the downstream mTOR/S6K signaling pathway. Thus, it can be assumed that bufalin inhibits CaMKIV by directly inhibiting the activity of CaMKKβ, thereby affecting its downstream mTOR/S6K signaling pathway to exert its anti-tumor effect. This research intends to study in vitro and in vivo perspectives that bufalin regulates the CaMKKβ/CaMKIV axis to inhibite mTOR/S6K signaling pathway to exert its anti-tumor mechanism. This study will explain the anti-tumor mechanism of bufalin which might suggest the new drug and target for ICC therapy.