DJ-1 促进 U87-MG 神经胶质瘤细胞系中的干细胞自我更新。

DJ-1 Contributes to Self-renewal of Stem Cells in the U87-MG Glioblastoma Cell Line.

机构信息

Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan

Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.

出版信息

Anticancer Res. 2019 Nov;39(11):5983-5990. doi: 10.21873/anticanres.13803.

DOI:10.21873/anticanres.13803

PMID:31704823

Abstract

BACKGROUND/AIM: DJ-1, an oncogenic molecule, helps to maintain somatic stem cells by reducing the intracellular level of reactive oxygen species (ROS). This study investigated the role of DJ-1 in glioma stem cells (GSCs).

MATERIALS AND METHODS

U87-MG (U87) and U251-MG (U251) glioblastoma cell lines that express wild-type and mutant p53, respectively, were used. These were cultured with DJ-1-targeting siRNA and subjected to a variety of in vitro experiments or intracranial transplantation into nude mice.

RESULTS

Knockdown of DJ-1 reduced clonogenicity only in U87 cells, which was rescued by p53 depletion. ROS accumulated in DJ-1-depleted cells, although treatment with N-acetyl cysteine, which quenches ROS, did not affect exhaustion of CSCs among U87 cells by DJ-1 knockdown. In a serial transplantation study, DJ-1 knockdown prolonged the survival of mice in secondary transplantation.

CONCLUSION

DJ-1 plays a pivotal role in maintenance of stem cell self-renewal in the U87 cell line.

摘要

背景/目的：DJ-1 是一种致癌分子，通过降低细胞内活性氧（ROS）的水平，有助于维持体干细胞。本研究探讨了 DJ-1 在神经胶质瘤干细胞（GSCs）中的作用。

材料和方法

使用分别表达野生型和突变型 p53 的 U87-MG（U87）和 U251-MG（U251）胶质母细胞瘤细胞系。这些细胞用 DJ-1 靶向 siRNA 处理，并进行各种体外实验或颅内移植到裸鼠中。

结果

DJ-1 敲低仅在 U87 细胞中降低集落形成能力，而 p53 耗竭可挽救这一作用。DJ-1 耗竭的细胞中 ROS 积累，但用 N-乙酰半胱氨酸（一种淬灭 ROS 的物质）处理并不影响 DJ-1 敲低导致 U87 细胞中 CSCs 耗竭。在一系列移植研究中，DJ-1 敲低延长了二次移植中小鼠的存活时间。