胶质瘤干细胞是恶性胶质瘤易复发、难治愈的重要原因之一。我们研究发现miR-125b抑制剂能有效抑制胶质瘤干细胞的生长和侵袭, 并参与调控PI3K/AKT、Bcl-2/Bax-Caspase 3和MMPs/TIMP等多条癌信号通路。深入研究发现它可增强脱甲氧基姜黄素(DMC)、替莫唑胺(TMZ)对胶质瘤干细胞的敏感性；DMC亦可通过抑制ABCG2基因增敏TMZ，而ABCG2基因又受miR-125b调控。据此，我们提出假说：miR-125b抑制剂→DMC→TMZ存在逐级放大的增敏效应，并通过miR-125b参与的上述癌信号通路调控胶质瘤干细胞增殖、侵袭和凋亡进程。本项目拟通过建立原代胶质瘤干细胞体外培养及颅内种植的模型，进行增殖、侵袭、凋亡等多方面抗肿瘤实验，深入探讨miR-125b抑制剂增敏DMC和TMZ的分子机制，为明确胶质瘤发病的新机制和防治策略提供理论依据。

Malignant glioma is one of the highest degree of human intracranial malignancy tumors, which is easy to recur, but difficult to cure. Nowadays, the presence of glioma stem cells is considered to be one of its main reasons. We found that miR-125b inhibitors can effectively inhibit the primary glioma stem cells growth and invasion, and its mechanisms are mediated by PI3K/AKT signaling pathway inhibition, Bcl-2/Bax-Caspase 3 pathway activation and MMPs/TIMP pathway inhibition.We also observed that it can sensitize glioma stem cells to demethoxycurcumin (DMC) and temozolomide (TMZ)；DMC can also enhance the chemosensitivity of TMZ by inhibiting ABCG2 gene expression while the ABCG2 gene is regulated by miR-125b expression. Accordingly, we hypothesize: the process of miR-125b inhibitor → DMC → TMZ exists progressively enlarged sensitizing effects, and miR-125b takes part in the signaling pathway involving proliferation, invasion and apoptosis process of glioma stem cells. This project intends to establish the primary glioma stem cells in vitro and intracranial planted model, and finish the anti-tumor experiments of proliferation, invasion and apoptosis, and so on. And further explore the molecular mechanisms of the above enhanced chemosensitivity by the regulation of miR-125b in order to provide a theoretical basis for the new mechanisms and prevention strategies on gliomas.