中文摘要
胶质瘤对化疗药物的耐受性是术后肿瘤复发、生存期缩短的重要原因。但传统的肿瘤耐药性研究仅关注于肿瘤本身,忽略了肿瘤微环境尤其是肿瘤基质细胞的影响。大量文献证实肿瘤基质细胞介导肿瘤耐药性的产生,而星形细胞在脑基质细胞中数目最多,分布最广,是胶质瘤微环境中最为独特的基质细胞群。研究表明胶质瘤间质星形细胞在胶质瘤的生长、侵袭过程中起重要作用,但其对胶质瘤耐药性的影响目前尚无系统研究。我们的前期实验发现肿瘤周围活化的星形细胞明显增强胶质瘤细胞对化疗药物替莫唑胺的耐受性,但其机制尚不明确。我们拟通过体外共培养实验、悬浮芯片法、基因芯片技术和临床样本分析,系统阐述胶质间质星形细胞介导肿瘤耐药性产生的机制,有望为胶质瘤的临床治疗,特别是在化学药物治疗中避免耐药性的产生、增强化疗药物敏感性,提供新的靶点和理论依据。
英文摘要
Glioma's resistance to chemotherapy is a major cause of its recurrence as well as reduced survival. The conventional research on resistance of tumors only focused on tumor itself. On the other hand, tumor microenvironment, especially the tumor stromal cells, has a major influence. Accumulating evidence shows the tumor stromal cells mediate the generation of the tumor's chemoresistance. Astrocytes are an unique group of stromal cells in glioma microenvironment, with the maximum number and widest distribution in the brain stromal cells. Glioma stromal astrocytes play an important role in growth and invasion of glioma, however, few studies focused on the role of the astrocytes in the chemoresistance of glioma. Our data showed that activated astrocytes in glioma could enhance glioma's resistance to chemotherapeutic temozolomide, but the mechanism is unknown. Hereby, we plan to apply in vitro coculture systems, suspension arrays, gene chips and clinical samples to uncover the underlying mechanism. Understanding this mechanism will provide both new thearpeutic target and thereotical basis for management of glioma, especially avoiding resistance and enhaning sensitvity in chemotherapy.
结题摘要
胶质瘤对化疗药物的耐受性是术后肿瘤复发、生存期缩短的重要原因。但传统的肿瘤耐药性研究仅关注于肿瘤本身,忽略了肿瘤微环境尤其是肿瘤基质细胞的影响。大量文献证实肿瘤基质细胞介导肿瘤耐药性的产生,而星形细胞在脑基质细胞中数目最多,分布最广,是胶质瘤微环境中最为独特的基质细胞群。本研究表明胶质瘤间质星形细胞在胶质瘤的生长、侵袭过程中起重要作用。我们的实验发现肿瘤周围活化的星形细胞明显增强胶质瘤细胞对化疗药物替莫唑胺的耐受性,进而通过体外共培养实验、悬浮芯片法、基因芯片技术、基因敲除肿瘤动物模型和临床样本分析,阐述了胶质间质星形细胞介导肿瘤耐药性产生的机制,有望为胶质瘤的临床治疗,特别是在化学药物治疗中避免耐药性的产生、增强化疗药物敏感性,提供新的靶点和理论依据。
