化疗在乳腺癌治疗中发挥着重要作用，然而，多药耐药的产生极大阻碍了化疗药物疗效。因此，筛选鉴定乳腺癌耐药标志物，阐明其在乳腺癌耐药中的功能，利用结构生物学信息，预测活性作用位点，以设计发现特异性的靶向抑制剂是目前亟待解决的问题。我们已成功建立人乳腺癌紫杉醇耐药细胞系，发现Transgelin 2是乳腺癌耐药分子靶标，但其在乳腺癌耐药中的生物学功能及调控模式尚未完全明确，Transgelin 2的活性作用位点未知，相应的特异性先导化合物难以发现。本项目是既往工作的深入，拟通过多种分析手段从体外、体内及临床三种水平探讨Transgelin 2异常表达调控乳腺癌多药耐药的功能机理；并利用结构生物学信息，应用分析化学等手段研究小分子化合物与Transgelin 2作用模式，联合分子对接方法分析Transgelin 2的活性作用位点，为创新性乳腺癌耐药相关先导化合物的发现及研究奠定基础。

Chemotherapy plays a very important role in the comprehensive treatment of breast cancer. However, the occurrence of multidrug resistance (MDR) greatly hindered the efficacy of chemotherapy drugs. Therefore, screening and identification of breast cancer resistance markers to clarify its functions and signal modes in the regulation of drug resistance in breast cancer. Using structural biology information of proteins predicts the active sites of action in order to design specific targeted inhibitors, which is considered the current problems to be solved. The previous study had successfully established paclitaxel multidrug resistant breast cancer cell line, finding that transgelin 2 was a MDR target for breast cancer therapy. However, the active sites of transgelin 2 were not entirely clear, leading that its specific lead compounds were hardly discovered. This study aimed to further determine the functional mechanism of MDR regulated by the abnormal expression of transgelin 2 in breast cancer from vitro, vivo and clinical three levels using molecular biology analysis methods. Base on structural biology information, the binding mode of small molecule compounds with transgelin 2 will be studied using analytical chemistry methods, and combined with molecular docking to foretell active sites of transgelin 2, which is promising to lay the foundation of innovative breast cancer resistant associated lead compounds.