HER2阳性乳腺癌曲妥珠单抗耐药是临床常见难题，HER2阳性乳腺癌细胞过表达的某些分子是发生耐药的重要机制。我们的前期研究揭示柴胡提取物可逆转曲妥珠单抗耐药，根据网络药理学研究方法预测柴胡皂苷类化学成分可能通过靶向DDX5逆转HER2阳性乳腺癌曲妥珠单抗耐药。我们初步研究发现，DDX5在曲妥珠单抗耐药细胞中的表达明显高于亲本细胞，下调DDX5可抑逆转耐药。本项目拟阐明靶向DDX5柴胡皂苷逆转HER2阳性乳腺癌曲妥珠单抗耐药作用的分子机制，同时运用多种手段活性靶向DDX5深入探讨中药柴胡中的活性物质，为把靶蛋白DDX5和柴胡皂苷转化为HER2阳性乳腺癌精准治疗的新靶点和新药物提供理论和实验依据。

Trastuzumab resistance in HER2 postive breast cancer is a common problem in clinical practice. Dysregulation of some molecules in breast cancer cell is one of the most important mechanisms. The previous research had illustrated that the extract could reverse rastuzumab resistance in HER2 positive breast cancer. Base on the network pharmacology, it predicted that saikosaponins could reverse rastuzumab resistance in HER2-positive breast cancer by targeting the DDX5. Our previous study also suggested that DDX5 was upregulated in trastuzumab-resistanct breast cancer cells and downregulation of DDX5 could re-sensitize breast cancer cells to trastuzumab. This project intends to clarify the molecular mechanisms of saikosaponins reversing rastuzumab resistance in HER2 positive breast cance by targeting DDX5. At the same time, we would discuss the active ingredients targeting DDX5 from Radix Bupleuri by using a variety of means. The research could provide theoretical and experimental basis for turning protein DDX5 and saikosaponins into new targets and drugs.