双氢青蒿素抑制神经胶质瘤干细胞治疗胶质瘤的作用及机制研究

Glioma poses great threat to people's health, whose treatment is still a worldwide clinical problem. The most malignant glioblastoma has become an important scientific obstacle during the glioma treatment because of its high invasiveness, easiness to get resistant to traditional radiotherapy & chemotherapy and the concomitant poor prognosis, all of which could be attributed to the existence of the glioma stem cells in glioblastoma tissue. Glioma stem cells has become the new strategy for glioma therapy in recent years. It is reported that inhibition of glioma stem cells can effectively inhibit the malignant glioma's growth. Our previous study found that Dihydroartemisinin could significantly inhibit the U87MG and U251MG cells growth and proliferation; moreover, we found Dihydroartemisinin could significantly inhibit the growth of the glioma stem cells exist in the primary glioma PGCSM-1 cell line; we also found in stem cells of the PGCSM-1 cells that Dihydroartemisinin could significantly decrease the expression of HES1 protein, the important downstream target of Notch pathway (one of the most important pathways that maintain the stemness of the glioma stem cell). Our project hence are designed to systematically investigate the effects and mechanisms by which Dihydroartemisinin inhibits the glioma stem cells and gloma growth through the Notch pathway in vitro and in vivo, based on our these preliminary findings. As far as we known, there is no studies of "artemisinin compounds" & "glioma stem cells inhibition" were reported on Pubmed. Our investigations will clarify the molecular mechanisms by which Dihydroartemisinin inhibits the glioma stem cells in glioma treatment, to provide new insights and therapeutic strategies for the future glioma therapy.

神经胶质瘤严重威胁人们健康，其治疗仍是世界性难题。恶性胶质瘤因其组织中存在胶质瘤干细胞而具有高浸润性、易对传统放/化疗产生耐受而预后差，这是胶质瘤临床治疗中亟待解决的重要科学问题。近年来胶质瘤干细胞成为胶质瘤治疗的新策略。研究表明抑制胶质瘤干细胞可有效抑制恶性胶质瘤生长。我们前期研究发现双氢青蒿素能显著抑制U87MG/U251MG细胞的生长增殖；重要的是还发现其能显著抑制原代神经胶质瘤PGCSM-1细胞中干细胞的生长数量、并显著降低(PGCSM-1)干细胞中干细胞干性维持重要通路——Notch通路重要靶蛋白HES1的表达。本项目拟在这此前期基础上：从Notch通路入手体内外系统研究双氢青蒿素抑制胶质瘤干细胞、抑制胶质瘤的效果及机制。经文献检索，尚未见青蒿素类化合物抑制胶质瘤干细胞的相关报道。项目成果将明确青蒿素类化合物抑制胶质瘤干细胞、治疗胶质瘤的机制，为胶质瘤治疗提供新的治疗策略和思路。

神经胶质瘤严重威胁人们健康，其治疗仍是世界性难题。恶性胶质瘤因其组织中存在胶质瘤干细胞而具有高浸润性、易对传统放/化疗产生耐受而预后差，这是胶质瘤临床治疗中亟待解决的重要科学问题。近年来胶质瘤干细胞成为胶质瘤治疗的新策略。研究表明抑制胶质瘤干细胞可有效抑制恶性胶质瘤生长。我们前期研究发现双氢青蒿素能显著抑制U87MG/U251MG细胞的生长增殖；重要的是还发现其能显著抑制原代神经胶质瘤PGCSM-1细胞中干细胞的生长数量、并显著降低(PGCSM-1)干细胞中干细胞干性维持重要通路——Notch通路重要靶蛋白HES1的表达。.本项目拟在这此前期基础上：从Notch通路入手体内外系统研究双氢青蒿素抑制胶质瘤干细胞、抑制胶质瘤的效果及机制。经文献检索，尚未见青蒿素类化合物抑制胶质瘤干细胞的相关报道。项目成果将明确青蒿素类化合物抑制胶质瘤干细胞、治疗胶质瘤的机制，为胶质瘤治疗提供新的治疗策略和思路。