中文摘要
采用鼻咽癌细胞CNE-1为靶细胞，选择不同浓度的广西何首乌中获得的蒽醌类化合物GXHSWAQⅠ单体进行体外放射增敏实验，通过细胞放射生物学和分子生物学技术，确定GXHSWAQⅠ放射增敏作用的剂量及作用机制。建立体内放射增敏裸鼠移植瘤模型，探讨GXHSWAQⅠ在体内的放射增敏活性。采用Biacore生物分子间互作系统，研究 GXHSWAQⅠ与CNE-1细胞中特异结合蛋白相互作用。结果发现无细胞毒作用浓度的GXHSWAQⅠ对乏氧CNE-1细胞具有放射增敏作用，增敏比呈剂量依赖性。体内实验表明GXHSWAQⅠ对人鼻咽癌裸鼠移植瘤也具有放射增敏作用。增敏机理可能与调控KU70/80、Survivin 、hTERT 、HIF-1α、Stat1等基因的表达，抑制亚致死性损伤修复和诱导细胞凋亡，引起G2＋M期阻滞，提高细胞内活性氧含量有关。与GXHSWAQⅠ结合的靶蛋白可能分布在细胞膜上，为GXHSWAQⅠ放射增敏靶蛋白分离纯化提供理论依据。结果提示：肿瘤的放射抗拒和放射增敏受到多种基因的调控，其中与氧依赖基因调控网络密切相关，研究结果为放射增敏的基因网络调控、增敏药物靶点研究提供一条新的途径。
英文摘要
To observe the radiosititive effects of GXHSWAQⅠ monomer (an Anthraquinone compound extracted from Guangxi Polygonum multiflorum )on human nasopharyngeal carcinoma CNE-1 Cells in vitro and investigate the mechanism of radiosensitivity and the effective dose . Tumor-bearing model was established by injecting nasopharyngeal carcinoma cells to Nu/Nu nude mice and explored whether GXHSWAQⅠ can enhance the radiosensitivity of nasopharyngeal carcinoma-xenotransplantation. Using Biacore system of label-free surface plasmon resonance (SPR) based technology for studying biomolecular interactions in real time to explore GXHSWAQ Ⅰcompound interaction with protein target for radiosensitizers. The results show that there were effects radiosensitivity of CNE-1 cells exposed to GXHSWAQⅠ monomer in the no-cytotoxic concentrations. The sensitization enhancement ration increased in a dose-dependent manner . It also enhances radiosensitivity of human nasopharyngeal carcinoma transplanted in nude mice .The mechanism may be inhibiting cells repairing in the hypoxic environment, inducing cells apoptosis,causing G2/M block and increasing the content of ROS in the tumor cells. Compared with radiation alone group, radiation combined hypoxia group obviously enhanced the expression of KU70/80, Survivin and hTERT. KU70/80, Survivin and h
结题摘要
采用鼻咽癌细胞CNE-1为靶细胞，选择不同浓度的广西何首乌中获得的蒽醌类化合物GXHSWAQⅠ单体进行体外放射增敏实验，通过细胞放射生物学和分子生物学技术，确定GXHSWAQⅠ放射增敏作用的剂量及作用机制。建立体内放射增敏裸鼠移植瘤模型，探讨GXHSWAQⅠ在体内的放射增敏活性。采用Biacore生物分子间互作系统，研究 GXHSWAQⅠ与CNE-1细胞中特异结合蛋白相互作用。结果发现无细胞毒作用浓度的GXHSWAQⅠ对乏氧CNE-1细胞具有放射增敏作用，增敏比呈剂量依赖性。体内实验表明GXHSWAQⅠ对人鼻咽癌裸鼠移植瘤也具有放射增敏作用。增敏机理可能与调控KU70/80、Survivin 、hTERT 、HIF-1α、Stat1等基因的表达，抑制亚致死性损伤修复和诱导细胞凋亡，引起G2＋M期阻滞，提高细胞内活性氧含量有关。与GXHSWAQⅠ结合的靶蛋白可能分布在细胞膜上，为GXHSWAQⅠ放射增敏靶蛋白分离纯化提供理论依据。结果提示：肿瘤的放射抗拒和放射增敏受到多种基因的调控，其中与氧依赖基因调控网络密切相关，研究结果为放射增敏的基因网络调控、增敏药物靶点研究提供一条新的途径。