肿瘤干细胞相关通路是癌症药物研发的有效靶点。课题前期研究发现天然产物木犀草素(Luteolin)具有如下活性：1)抑制前列腺癌细胞干性、EMT并增强对恩扎鲁胺(enzalutamide)的敏感性；2)上调FZD6抑制β-catenin的转录活性；3）抑制miR-130的表达且miR-130靶向FZD6。因此，课题假设：Luteolin通过miR-130/FZD6/β-catenin通路轴抑制前列腺癌细胞的干性和EMT，增强enzalutamide药物敏感性。课题将进一步利用慢病毒基因调控系统、原代3D微球培养、临床样本异种移植小鼠模型(PDX)等技术证明miR-130/FZD6/β-catenin通路轴：1)在前列腺癌中的重要角色及临床意义；2)为Luteolin抑制前列腺癌干性和EMT的主要分子靶点。本课题将为Luteolin精准治疗此通路轴异常激活前列腺癌亚型提供理论依据。

Cancer stem cell is the leading cause of prostate cancer initiation, progression, metastasis and chemoresistance. Forced regulation of signaling pathway involved in stemness is effective strategy against prostate cancer. We previously found that: 1) Luteolin, a natural product, inhibits prostate cancer cell stemness and EMT, sensitizes the cells to enzalutamide; 2) Luteolin inhibits Wnt signaling pathway by upregulation of FZD6; 3) Luteolin inhibits the expression of miR-130, which negatively regulates FZD6 expression as the result of bioinformatics analysis. We therefore postulate that luteolin regulates prostate cancer stemness, EMT and chemosensitivity by inhibiting miR-130/FZD6/β-catenin axis. Next, we will reveal 1) the role of miR-130/FZD6/β-catenin axis in prostate cancer and 2) suppressing miR-130/FZD6/β-catenin axis is the mechanism-of-action of luteolin regulating prostate cancer stemness, EMT and chemosensitivity. Our work will offer a theoretical basis for Luteolin precision treatment of prostate cancer subtypes caused by aberrant activation of miR-130/FZD6/β-catenin axis.