乳腺癌干细胞（BCSCs）是乳腺癌复发转移的根源，研究表明BCSCs干性与Hedgehog（Hh）通路密切相关，该通路核转录因子Gli激活可引起乳腺癌细胞上皮间质转化（EMT）。我们前期研究发现姜黄素能降低BCSCs悬浮球形成能力及CD44+CD24-细胞亚群，抑制干细胞基因，调节 EMT标志物表达。由此我们推测BCSCs与贴壁细胞存在EMT相关高度差异表达关键基因；姜黄素可能通过Hh/Gli通路靶向BCSCs调控EMT进程阻止癌转移。本项目首次应用EMT基因PCR芯片分析BCSCs的EMT特征，继而体外研究姜黄素是否通过Hh通路分子靶向调节BCSCs干性及EMT；并创新性应用慢病毒载体构建稳定表达荧光素酶BCSCs-luc2，制备乳腺癌肺转移裸鼠模型，小动物活体成像追踪观察姜黄素对BCSCs-luc2荷瘤裸鼠肿瘤生长及转移干预作用并研究其分子机制，为姜黄素在乳腺癌转移领域的应用奠定基础。

Breast cancer stem cells (BCSCs) are the origin of breast cancer recurrence and metastasis. Studies showed that proliferation and stemness maintenance of BCSCs are closely correlated to the Hedgehog (Hh) signaling pathway. Activation of downstream nuclear transcription factor of Hh pathway Gli can cause EMT in breast cancer cells. Our previous study found that curcumin reduced BCSCs suspension mammospheres formation and differentiation ability and the stem cell surface marker CD44 +CD24- / low cell subpopulation, effectively inhibiting its stemness features and epithelial-mesenchymal transition (EMT). Therefore, we hypothesize that the genes regulate EMT exist great difference between BCSCs and the adherent parental cells and curcumin may prevent breast cancer metastasis by regulating the Hh/Gli signaling pathway and inhibiting the progression of BCSCs and EMT. In this project, EMT gene expression PCR chips were used to comprehensively detect the EMT characteristics of BCSCs for the first time. Then in vitro, curcumin modulates the function of BCSCs and EMT through Hh signaling pathway-related molecules and use lentiviral vector to construct BCSCs-luc2 cell line with stable expressed luciferase to prepare nude mice model with breast cancer lung metastasis. Small animal living imaging technology will be used to observe the effect of curcumin on tumor growth and metastasis of BCSCs-luc2 tumor-bearing nude mice and to explore its molecular mechanism. It is helpful for us to find targets of curcumin on breast cancer metastasis and to lay the experimental foundation for the research and application of curcumin in the field of breast cancer metastasis.