中文摘要
一般西医抗癌药物在杀伤肿瘤细胞同时也会对肝、肾、血液系统等产生不同程度的毒副作用。中药莪术提取物β-榄香烯与前者不同,其毒副作用小而抗瘤效应强,且能穿透血脑屏障,是一种较为理想的脑癌治疗药物。我们前期研究发现β-榄香烯除对恶性胶质瘤细胞有较强杀伤作用外,还能诱导产生自噬,同时可以调节机体T细胞亚群功能;另外,我们在对维生素E类似物α-TEA的研究中发现,自噬介导的抗原交叉提呈在抗肿瘤免疫反应中存在重要作用。由此,我们提出如下假说:榄香烯诱导的自噬可通过抗原交叉提呈从而产生整体抗肿瘤免疫效应。为证实此假说,本项目拟:1、探讨榄香烯诱导胶质瘤细胞产生自噬的机制;2、探究树突状细胞负载自噬体后在体外/体内条件下激活CD8+ T细胞产生免疫应答的效果;3、研究树突状细胞负载自噬体后的整体抗瘤活性及其机制。上述研究旨在阐明榄香烯的抗肿瘤免疫效应机制,为进一步拓展其抗胶质瘤的临床应用提供科学依据。
英文摘要
Different from routine chemotherapeutic durgs that control tumor growth by dirct killing of individual tumor cells, antitumor Chinese Traditional Medicine could boost the immune response of the patient with the exact mechnism remains unclear. β-elemene, a compound that derived from RhizomaZedoariae, is capable of passing the brain blood barrier, and has already been used in the treatment of several malignancies including gliomas. We have previously showed β-elemene was capable of killing glioma cells through activating apoptotic pathway and, more recently, inducing glioma cells autophagy. On the other hand, we also has discovered the autophagosom derived from alpha-tocopheryloxyacetic acid treated tumor cells could stimulate efficient antigen cross-presentation and lead to activation of anti-tumor immune response. Therefore, we hypothesize the induction of autophagy in glioma cells by β-elemene could activate the host immune system via antigen cross-presentaiton to CD8+ T cells. To test this hypothesis, we designed the following studies: 1) to elucidate the mechanism by which β-elemene could induce autophagy in glioma cells in vitro; 2) to determine the in vitro and in vivo efficacy of autophagosomes-pulsed dendrite cells on CD8+ T cells activations; 3) to test the in vivo antitumor efficacy of dendrite cells vaccination. We believe these efforts would be valuable for illuminations of the mechnisms by which β-elemene strengthens the host immune system and supporting its clincial appplicaitons in the field of anti-glioma treatments.
