丙戊酸钠对人胶质瘤干细胞增殖和凋亡的影响

发布时间：2018-04-04 02:06

本文选题：丙戊酸钠　切入点：胶质瘤干细胞　出处：《基因组学与应用生物学》2017年06期

【摘要】：胶质瘤干细胞是胶质瘤起源和化疗抵抗的重要原因,也是胶质瘤治疗的重要靶点。丙戊酸钠是一种去乙酰化酶抑制剂,具有抗肿瘤活性。本研究主要探讨丙戊酸钠对胶质瘤干细胞生长的影响。我们使用无血清培养方法从A172胶质瘤细胞中,分离培养胶质瘤干细胞,免疫荧光染色发现胶质瘤干细胞表达Nestin和CD133。使用不同浓度(0.5~1.5 mmol/L)丙戊酸钠连续处理胶质瘤干细胞7 d,CCK8检测细胞活力,从第4天起,就可观察到丙戊酸钠处理组细胞OD值显著低于正常组,并且随着丙戊酸钠浓度的增加和处理时间的延长,细胞OD值下降更为明显。检测胶质瘤干细胞克隆形成率,正常组胶质瘤干细胞在干细胞培养基中培养7 d后,克隆形成率为(21±2.03)%,给予0.5 mmol/L丙戊酸钠处理胶质瘤干细胞,克隆形成率明显下降到(13±3.86)%,继续增加丙戊酸钠浓度至1 mmol/L或1.5 mmol/L时,克隆形成率分别非常显著下降至(10±4.71)%和(8±3.66)%。此外,丙戊酸钠也可导致胶质瘤干细胞凋亡,并且细胞凋亡率随着丙戊酸钠浓度的增加而增加。本研究证实丙戊酸钠抑制胶质瘤干细胞增殖和凋亡,并且其抑制效应具有浓度依赖性。丙戊酸钠是一种非常有潜力的治疗胶质瘤的药物,本研究的完成将为它的临床运用提供坚实的理论基础。
[Abstract]:Glioma stem cells are an important cause of glioma origin and chemotherapeutic resistance, and also an important target of glioma therapy.Sodium valproate is a deacetylase inhibitor with anti-tumor activity.The aim of this study was to investigate the effect of sodium valproate on the growth of glioma stem cells.We isolated and cultured glioma stem cells from A172 glioma cells by serum-free method. Immunofluorescence staining showed that glioma stem cells expressed Nestin and CD133.The cell viability was measured with sodium valproate at different concentrations of 0.5 mmol / L (1.5 mmol / L) for 7 days after continuous treatment with sodium valproate. From the 4th day, it was observed that the OD value of the cells treated with sodium valproate was significantly lower than that of the normal group.With the increase of sodium valproate concentration and the prolongation of treatment time, the OD value of cells decreased more obviously.The colony forming rate of glioma stem cells was detected. After cultured in stem cell culture medium for 7 days, the colony forming rate of glioma stem cells in normal group was 21 卤2.03.The glioma stem cells were treated with 0.5 mmol/L sodium valproate.When the concentration of sodium valproate was increased to 1 mmol/L or 1.5 mmol/L, the clone formation rate decreased significantly to 10 卤4.71% and 8 卤3.66%, respectively.In addition, sodium valproate also induced apoptosis of glioma stem cells, and the apoptosis rate increased with the increase of sodium valproate concentration.This study confirmed that sodium valproate inhibited the proliferation and apoptosis of glioma stem cells in a concentration dependent manner.Sodium valproate is a promising drug for the treatment of glioma, and this study will provide a solid theoretical basis for its clinical application.
【作者单位】：解放军第四五一医院神经内科;西安市第五医院内一科;解放军第三二三医院疼痛科;西北大学生命科学学院;第三军医大学西南医院神经外科;
【基金】：陕西省科学技术研究自然基金(2013JM4006) 兰州军区医药卫生科研计划项目(CLZ13JB18) 第三二三医院2012年度培育课题(2012323A01)共同资助
【分类号】：R739.41

【参考文献】