文章：

14-3-3 -3zeta下调可抑制人胶质母细胞瘤的增殖，增加细胞凋亡

Down-regulation of 14-3-3zeta reduces proliferation and increases apoptosis in human glioblastoma

原文发布日期：2019-05-09 

英文摘要：

Many efforts have been taken to develop molecule target for cancer therapy. 14-3-3zeta protein has emerged as a critical regulator of diverse cellular pathways in multiple cancers. Furthermore, 14-3-3zeta expression was elevated and a predictor of poor prognosis in glioblastoma. However, there is no information to evaluate the potential effects of 14-3-3zeta RNAi in glioblastoma. The relationship between 14-3-3zeta expression and cell proliferation and apoptosis was tested in primary glioblastoma samples. Through an RNAi approach using human glioblastoma cells as a model system, we demonstrated the role of 14-3-3zeta in glioblastoma proliferation, apoptosis, invasion and tumor growth. The expression of 14-3-3zeta in glioblastoma stem cells was also investigated by immunostaining. The apoptosis was significantly higher in 14-3-3zeta-negative group than in positive group. 14-3-3zeta immunoreactivity score was negatively correlated with the apoptosis, and positively with proliferation in human specimens. 14-3-3zeta RNAi reduced cell proliferation, induced apoptosis, decreased the invasive capability and colony-formation, and impaired the growth of glioblastoma xenografts in nude mice. Moreover, 14-3-3zeta was positively expressed in glioblastoma stem cells. Our data highlight the importance of 14-3-3zeta in glioblastoma and identify 14-3-3zeta as a potential molecular target for glioblastoma treatment.

摘要翻译： 

为开发癌症治疗的分子靶点，研究者已付出诸多努力。14-3-3ζ蛋白在多种癌症中已成为细胞通路的关键调控因子，且在胶质母细胞瘤中其表达水平升高，可作为预后不良的预测指标。然而，关于14-3-3ζ RNA干扰在胶质母细胞瘤中潜在作用的评估尚属空白。本研究通过检测原代胶质母细胞瘤样本中14-3-3ζ表达与细胞增殖、凋亡的关系，并采用RNA干扰技术以人胶质母细胞瘤细胞为模型，证实了14-3-3ζ在肿瘤增殖、凋亡、侵袭及体内生长中的调控作用。通过免疫组化检测发现，14-3-3ζ阴性组的细胞凋亡率显著高于阳性组。人类组织标本分析显示：14-3-3ζ免疫反应评分与凋亡呈负相关，与增殖呈正相关。RNA干扰实验表明，抑制14-3-3ζ表达可降低细胞增殖、诱导凋亡、减弱侵袭能力与克隆形成，并显著抑制裸鼠移植瘤生长。此外，胶质母细胞瘤干细胞中14-3-3ζ呈阳性表达。本研究揭示了14-3-3ζ在胶质母细胞瘤中的关键作用，并确立其作为潜在治疗靶点的价值。

原文链接：

Down-regulation of 14-3-3zeta reduces proliferation and increases apoptosis in human glioblastoma