如何抑制肝内胆管癌（ICC）是临床肝恶性肿瘤治疗领域亟待解决的难题。课题组的研究及已有报道显示，神经元细胞-癌细胞间NE/ADRB2/NGF/TrkA正反馈环路在ICC发展恶化进程中至关重要。逍遥散（XYS）在临床被广泛用于肝胆疾病治疗，被证实能逆转肝郁气滞患者的临床症状（交感神经偏亢、精神抑郁等）。前期预实验发现，逍遥散联合吉西他滨在体内可有效抑制神经元细胞与癌细胞共同接种的移植瘤，同时能下调条件培养基诱导的ADRB2、NGF（癌细胞中）和TrKA和NE（神经元细胞中）水平，但机制不明。本项目拟在体内外水平对逍遥散联合吉西他滨抑制ICC的效应进行确证；运用分子生物学手段，挖掘逍遥散对神经元细胞-癌细胞间正反馈环路的调节作用与其抑制效应的相关性；采用通路调节剂探讨逍遥散调控该通路的分子机制。本项目有助于揭示逍遥散对ICC的抑制效应及分子机制，为其与吉西他滨联合治疗ICC的应用提供药理学依据

How to inhibit intrahepatic cholangiocarcinoma (ICC) is an urgent problem in the treatment of primary hepatic malignancy. Our previous studies have shown that NE/ADRB2/NGF/TrkA regenerative feedback loop between neuronal and cancer cells played an important role in the development and progression of ICC. Xiaoyaosan (XYS) has been approved for treatment of hepatic and gall diseases, and it has been proved to be able to reverse the clinical symptoms of patients with liver depression and qi stagnation (sympathetic hyperactivity, mental depression, emotional unrest). Our pre-experimental found that XYS combined with gemcitabine can effectively inhibit the transplanted tumor inoculated by neuronal cells and ICC cells in vivo while reduce effective the expression of ADRB2, NGF in cancer cells and TrkA, NE in neuronal cells, respectively. However, the underlying mechanism is unclear. In this study, we will (1) use ingenious animal and cell model to confirm the inhibitory effect of XYS combined with gemcitabine on ICC; (2) use various molecular biological methods combined with genetic techniques to study the relationship between the inhibitory effect of XYS on ICC and its regulation on NE/ADRB2/NGF/TrkA regenerative feedback loop; (3) use pathway inhibitor/agonist to explore the regulation mechanism of XYS on NE/ADRB2/NGF/TrkA regenerative feedback loop between neuronal and cancer cells. Our project will elucidate the effect and molecular mechanism of XYS on ICC, and will provide scientific basis for the drug curative combination of XYS and gemcitabine on ICC in clinical.