在乳腺癌的进展过程中乳腺上皮细胞周围基质会发生显著的改变，纤连蛋白（FN）表达上调是其关键变化之一。FN可诱导乳腺上皮细胞发生间质转化（EMT）促进乳腺癌的发展。此外，calpain (CANP)/calpastatin (CST)系统失调在乳腺癌的进展中也起着重要作用。本课题组前期研究发现，FN在诱导乳腺上皮细胞发生EMT的同时，使CANP表达上调，CST表达下调，可能存在该系统的失调，黄芩素能抑制这一变化。在本项目中，以FN诱导乳腺上皮细胞EMT为研究对象，考察黄芩素对这一过程的干预作用，并研究黄芩素对CANP和CST表达、分布、活性以及其上游ERK和钙离子信号通路的影响，阐明黄芩素通过调控CANP/CST系统，抑制FN诱导EMT的机制；并通过自发乳腺癌小鼠模型，在整体水平验证体外实验结果。本项目为深入探索黄芩素防治乳腺癌的机制提供新的依据，也为抗乳腺癌药物的研究提供新靶点和新思路。

In the mammary gland, the stromal extracellular matrix undergoes dramatic changes during breast cancer tumorigenesis and development. High level of fibronectin (FN) and its ability to induce epithelial-mesenchymal transition (EMT) of breast epithelium show an active role in breast cancer progression. The deregulation of the calpain/calpastatin system could drive breast cancer development. Our preliminary results showed that the expression of calpain 1 and calpain 2 were up-regulated, yet the expression of calpastatin was down-regulated during FN-induced EMT of mammary epithelial cells, but baicalein suppressed this changes of calpain and calpastatin expression. In this study, we evaluated the effect of baicalein on FN-induced EMT of mammary epithelial cells. In addition, to determine whether baicalein could take effect of calpain/calpastatin system, we will detect the expression, subcellular distribution and activity of calpain and calpastatin, as well as their upstream signaling pathway including extracellular signal-regulated kinase (ERK) and calcium ion signaling. Moreover, the MMTV-PyMT mice model with highly aggressive spontaneous mammary tumors will be used to validate the results of the in vitro studies. In general, our project may provide new evidence for clarifying the mechanism of baicalein in breast cancer prevention and treatment. Furthermore it may offer a new target and an approach for drug discovering of breast cancer.