从miR-200c介导的Notch信号通路研究增免抑瘤方及有效组分抑制卵巢癌干细胞侵袭转移的作用机制

增免抑瘤方（ZMYL）为治疗卵巢癌的经验方，用于临床治疗取得了满意疗效，但该方治疗卵巢癌具体作用途径与机理尚不清楚。卵巢癌干细胞（OCSCs）的存在是卵巢癌复发转移及化疗耐药的根源，卵巢癌干细胞侵袭转移的过程中发生了上皮间转化（EMT）。miR-200c介导的Notch信号通路在细胞的增殖、侵袭、转移等多种生物学行为中发挥重要作用。我们前期研究发现ZMYL可以逆转OCSCs发生EMT并抑制卵巢癌干细胞的增殖和转移。推测ZMYL可能是通过Notch信号通路调控OCSCs侵袭和转移达到抑制卵巢癌的进展。本课题拟在既往研究的基础上，体外培养卵巢癌细胞株SKOV3和肿瘤干细胞，构建高表达miR-200c的卵巢癌干细胞，探讨ZMYL及有效组分通过miR-200c介导的Notch通路抑制OCSCs侵袭和转移的分子机制，最后进行动物体内验证，为ZMYL临床治疗卵巢癌提供新的科学依据和理论基础。

ZMYL is used for the treatment of ovarian cancer in clinical practice and has obtained the satisfactory curative effect, but the mechanism and the specific pathway are still unclear. The existence of ovarian cancer stem cells (OCSCs) is the root cause of recurrence、metastasis and chemotherapy drug resistance of ovarian cancer, in the process of invasion and metastasis of ovarian cancer stem cells occurred epithelial-mesenchymal transition (EMT). MiRNA-200c can mediate the Notch signaling pathway which plays an important role in cell proliferation, invasion, metastasis and other biological behavior. Our previous study found ZMYL can reverse EMT and inhibit the proliferation and metastasis of OCSCs. So we peculated that ZMYL may regulate the invasion and metastasis of OCSCs through Notch signaling pathways to inhibit the progress of ovarian cancer. This project is proposed on the basis of previous study, culturing ovarian cancer cell lines SKOV3 and cancer stem cells in vitro, building a high expression of miR-200c ovarian cancer stem cells, to explore the molecular mechanisms of ZMYL and the effective components inhibiting the invasion and metastasis of OCSCs through Notch pathway mediated by miR-200c, and finally verified in vivo, to provide new scientific and theoretical basis for ovarian cancer clinical treatment by ZMYL.