双氢青蒿素下调NICD-1对胶质瘤增殖和凋亡的影响

发布时间：2018-01-19 20:42

本文关键词： 神经胶质瘤双氢青蒿素 Notch信号通路 NICD-1 增殖和凋亡　出处：《重庆医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的探讨双氢青蒿素(dihydroartemisinine,DHA)对人脑胶质瘤增殖和凋亡的影响及机制。方法1.人胶质瘤U251细胞株传代培养,设置空白对照组、DMSO组、DAPT组和DHA组(10、20、40、80μmol/L),应用CCK-8和FCM法检测细胞增殖、周期及早期凋亡,Western blot检测Notch1的胞内区域(NICD-1)及其下游靶蛋白Hes1的表达水平;2.建立裸鼠皮下胶质瘤模型(n=20),按随机数表将其随机分为DMSO对照组、DAPT组、DHA治疗组(50、100mg/kg),每组5只,根据时间体积曲线计算各组抑瘤率,免疫组化法检测裸鼠皮下移植瘤组织中NICD-1表达水平变化。结果1.与空白对照组和DMSO组相比,DHA组U251细胞增殖率显著下降,G1期细胞所占百分比显著上升,S期细胞所占百分比显著下降,早期凋亡率显著上升(P0.05),NICD-1及Hes1蛋白表达水平显著低于空白对照组(P0.05),均呈浓度依赖关系;2.DHA各治疗组的裸鼠皮下移植瘤生长速率及移植瘤组织内NICD-1表达显著低于DMSO对照组(P0.05)。结论DHA有效抑制人神经胶质瘤细胞增殖,促进其凋亡;其作用机制可能与通过下调NICD-1的表达,抑制Notch信号通路有关。
[Abstract]:Objective to study dihydroartemisinine dihydroartemisinine. The effect and mechanism of DHA on the proliferation and apoptosis of human glioma. 1. Human glioma U251 cell line was subcultured, and the blank control group was set up as DMSO group and DHA group. 2. CCK-8 and FCM were used to detect cell proliferation, cell cycle and early apoptosis. Western blot was used to detect the expression of NICD-1 in the intracellular region of Notch1 and its downstream target protein Hes1. 2. The model of subcutaneous glioma in nude mice was established and randomly divided into DMSO control group (n = 5) and DAPT group (n = 5). According to the time volume curve to calculate the tumor inhibition rate, immunohistochemical method to detect the expression of NICD-1 in nude mice subcutaneous transplanted tumor tissue. Results 1.Compared with the blank control group and DMSO group. 2. In DHA group, the proliferation rate of U251 cells decreased significantly; the percentage of cells in G 1 phase increased significantly; the percentage of S phase cells decreased significantly, and the early apoptosis rate increased significantly (P 0.05). The expression levels of NICD-1 and Hes1 protein were significantly lower than those of the control group (P 0.05), both in a concentration-dependent manner. 2. The growth rate of subcutaneous transplanted tumor and the expression of NICD-1 in xenografts of nude mice in DHA treatment group were significantly lower than those in DMSO control group (P0.05). Conclusion DHA can effectively inhibit the proliferation of human glioma cells. Promoting apoptosis; The mechanism may be related to the inhibition of Notch signaling pathway by down-regulating the expression of NICD-1.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.41

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