胶质瘤干细胞（GSCs）是恶性胶质瘤高复发率和死亡率主要原因之一，尚无有效治疗方法。申请人前期研究发现脱甲氧基姜黄素（DMC）可抑制GSCs增殖，但其生物利用度低，颅内效应差。为此，申请人通过结构修饰发现其衍生物DMC-BH420（专利公布号：201510180690.8）抗GSCs能力显著优于DMC，但其机制未明。申请人预研究证实DMC-BH420可诱导miR-145过表达，下调翻译控制肿瘤蛋白（TCTP），并激活Caspase-3等；并证明miR-145靶向调控TCTP表达，过表达TCTP可逆转DMC-BH420的抑瘤作用。据此，我们提出miR-145靶向调控TCTP可能是DMC-BH420抗GSCs的核心机制之一。本项目中，申请人将利用分子生物学及裸鼠原位移植瘤模型等方法，重点研究DMC-BH420体内外抗GSCs的作用及其分子机制，为开发其用于治疗胶质瘤提供理论和实验依据。

Glioma stem cells (GSCs) are one of the main causes of high recurrence rate and mortality of malignant gliomas, which have no effective treatments.Previous studies by us found that DMC could inhibit the proliferation of GSCs; however,its bioavailability was low and intracranial effect was poor. Therefore, a new type of derivative DMC-BH420 was developed by modifying the DMC structure (Patent Publication No.: 201510180690.8), and the results showed that DMC-BH420 was significantly better than DMC on anti-GSCs. But its mechanism of anti-GSCs was unknown.Our pre-experiment confirmed that DMC-BH420 could induce miR-145 overexpression, inhibit translationally controlled tumor protein (TCTP) expression, and activate Caspase-3 signaling pathway. Meanwhile, we also confirmed that miR-145 targeted regulation of TCTP, and upregulation of TCTP could reverse the inhibitory effect of DMC-BH420 on tumor growth. Thus, we propose that miR-145 targeting the activation of TCTP signaling pathway may be one of the key mechanisms of DMC-BH420 on anti-GSCs.In this project, the applicant will use the methods of molecular biology and orthotopic transplantation tumor model in nude mice to study the biological function and molecular mechanism of DMC-BH420 on anti-GSCs both in vivo and in vitro, and provide theoretical and experimental basis for glioma treatment.