中文摘要
乳腺癌远处转移是影响其预后的主要原因,上皮-间质转化(EMT)是导致转移的关键环节。中医认为气血两虚、瘀血阻滞是乳腺癌的主要症型,治疗上应以扶正活血为主。槐耳清膏具有活血消癥、扶正固本之功效,并已应用于乳腺癌临床治疗,但其活性成分,对乳腺癌转移的影响及具体调控机制不明。课题组前期研究发现:①槐耳清膏抑制乳腺癌细胞(BCCs)增殖,控制乳腺癌EMT;②EphB4蛋白过表达可激活PI3K/AKT/mTOR信号通路促进乳腺癌EMT。结合文献和前期研究基础,我们推测:槐耳清膏可能通过下调EphB4蛋白表达抑制PI3K/AKT/mTOR信号通路激活,从而抑制乳腺癌EMT,控制乳腺癌转移。为验证假说,本项目拟在乳腺癌细胞系和小鼠乳腺癌移植瘤模型上,探讨槐耳清膏对乳腺癌EMT的调控机制,揭示槐耳清膏抗乳腺癌EMT的科学内涵及其有效成分,以寻求抑制乳腺癌转移的新靶点和药物,为中医药防治乳腺癌提供新思路。
英文摘要
Distant metastasis of breast cancer is the major factor affecting prognosis, epithelial-mesenchymal transition(EMT) is key step of metastasis of breast cancer. Qi-blood deficiency and blood stasis are two main syndromes of advanced breast cancer in traditional Chinese medicine, so Fuzheng Guben should be the main way for the treatment of breast cancer. Coincidentally, the function of Huaier is known as Huoxue Xiaozheng, Fuzheng Guben, and has been verified clinically. Although Huaier is used in clinical medicine wildly, it is still not clear about the acting constituent in Huaier which obstruct EMT of breast cancer and the main mechanism. The preliminary study of our research group found that ①Huaier can inhibit proliferation of BCCs; ②the over-expression of protein EphB4 can promote the EMT of breast cancer by activating the pathway of PI3K/AKT/mTOR. According to previous researches, we speculate that Huaier can inhibit the activation of PI3K/AKT/mTOR pathway by down-regulating the expression of EphB4 to suppress EMT of breast cancer, in order to control the metastasis of it. To identify the hypothesis, we design this experiment which depends on the integrative theory of traditional Chinese medicine together with western medicine system. In which, we protocol to use breast carcinoma cell lines and mice models of breast cancer metastases, so as to discuss the regulatory mechanism of Huaier for inhibits the EMT of breast cancer, reveal the scientific connotation about how Huaier against breast cancer EMT and analyze the effective constituent of it. The aim of the experiment is to find out new target site and new drug which may act to reduce the metastasis of breast cancer, consequently to provide a new way for prevention and treatment of breast cancer by traditional Chinese medicine.
