论文部分内容阅读
目的探讨双氢青蒿素(dihydroartemisinine,DHA)对人神经胶质瘤生长的影响及机制。方法人胶质瘤U251细胞株传代培养,设置空白对照组、二甲基亚砜(DMSO)组、DAPT组和DHA(10、20、40、80μmol/L)实验组,应用CCK-8和FCM检测细胞增殖、周期及凋亡,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。建立裸鼠皮下胶质瘤模型(n=20),按随机数字表法分为DMSO组、DAPT组、DHA(50、100 mg/kg)治疗组,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。结果与空白对照组和DMSO组相比,实验组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(P<0.05),NICD-1及Hes1蛋白表达水平显著低于空白对照组(P<0.05),均呈浓度依赖关系;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(P<0.05)。结论 DHA有效抑制人神经胶质瘤的生长,其作用机制可能与通过下调NICD-1表达抑制Notch信号通路有关。
Objective To investigate the effect of dihydroartemisinine (DHA) on the growth of human glioma and its mechanism. Methods The human glioma U251 cell line was subcultured, and the control group, dimethyl sulfoxide (DMSO) group, DAPT group and DHA (10,20,40,80μmol / L) Cell proliferation, cell cycle and apoptosis were detected by Western blot. The expression of NICD-1 and its downstream target protein Hes1 were detected by Western blot. The nude mice model of subcutaneous glioma (n = 20) was established and divided into DMSO group, DAPT group and DHA group (50, 100 mg / kg) by random number table. The tumor inhibition rate and immunohistochemical method were used to detect the expression of NICD-1 in subcutaneously transplanted tumor tissue of nude mice. Results Compared with the blank control group and DMSO group, the proliferation rate of U251 cells in experimental group was significantly decreased, the percentage of cells in G1 phase increased significantly, the percentage of cells in S phase decreased significantly, the early apoptosis rate increased significantly (P <0.05) NICD-1 and Hes1 protein expression levels were significantly lower than the blank control group (P <0.05), were in a concentration-dependent manner; DHA treatment groups nude mice subcutaneous xenograft tumor growth rate and tumor tissue NICD-1 expression was significantly lower DMSO control group (P <0.05). Conclusion DHA can effectively inhibit the growth of human glioma. The mechanism may be related to the inhibition of Notch signaling pathway through the down-regulation of NICD-1 expression.