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FOXO4 的表达与胶质母细胞瘤的发生发展相关,FOXO4 的表达在体外和体内均能抑制细胞的恶性表型。

FOXO4 expression associates with glioblastoma development and FOXO4 expression inhibits cell malignant phenotypes in vitro and in vivo.

机构信息

Anatomy Experimental Center, Wannan Medical College, Wuhu 241002, Anhui, China; Graduate School of Wannan Medical College, Wuhu 241002, Anhui, China; Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu, China.

Graduate School of Wannan Medical College, Wuhu 241002, Anhui, China; Department of Neurosurgery, Yijishan Hospital, Wannan Medical College, Wuhu 241001, Anhui, China.

出版信息

Life Sci. 2020 Apr 15;247:117436. doi: 10.1016/j.lfs.2020.117436. Epub 2020 Feb 15.

Abstract

BACKGROUND AND AIM

Forkhead box protein O4 (FOXO4) is a transcription factor, and aberrant FOXO4 expression is associated with development of various human cancers. This study explored the role of FOXO4 in glioma in vitro and in vivo.

METHODS

FOXO4 expression was first assessed in normal brain tissues, low-grade glioma, glioblastoma multiforme (GBM), normal human astrocytes (HA), and GBM cell lines, while manipulation of FOXO4 expression in glioma cell lines was assessed using qRT-PCR, Western blot, and cell viability CCK-8, Transwell, and a nude mouse subcutaneous xenograft assays.

KEY FINDINGS

The data showed downregulated FOXO4 expression in GBM tissues and cell lines. FOXO4 overexpression induced by transfection with FOXO4 cDNA significantly inhibited GBM cell proliferation, migration, and invasion, but increased tumor cells to undergo apoptosis in vitro, while suppressed growth of GBM cell subcutaneous xenografts in nude mice. In conclusion, FOXO4 possesses an anti-cancer glioma activity, which could be a novel target for future control of GBM.

摘要

背景与目的

叉头框蛋白 O4(FOXO4)是一种转录因子,异常表达与多种人类癌症的发生发展有关。本研究探讨了 FOXO4 在体外和体内对神经胶质瘤的作用。

方法

首先评估了正常脑组织、低级别神经胶质瘤、胶质母细胞瘤(GBM)、正常人类星形胶质细胞(HA)和 GBM 细胞系中 FOXO4 的表达,并用 qRT-PCR、Western blot 和细胞活力 CCK-8、Transwell 以及裸鼠皮下异种移植实验评估了在神经胶质瘤细胞系中操纵 FOXO4 表达的情况。

主要发现

数据显示 GBM 组织和细胞系中 FOXO4 表达下调。通过转染 FOXO4 cDNA 过表达 FOXO4 显著抑制 GBM 细胞增殖、迁移和侵袭,但体外诱导肿瘤细胞凋亡,同时抑制裸鼠 GBM 细胞皮下异种移植的生长。总之,FOXO4 具有抗肿瘤神经胶质瘤活性,可能成为未来控制 GBM 的新靶点。

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