Li Xiaomei, Cai Limin, Chen Hui, Zhang Qingyuan, Zhang Shujun, Wang Yanhua, Dong Yanyan, Cheng Hui, Qi Jiping
Department of Pathology, Harbin Medical University, China.
Pathobiology. 2009;76(4):181-92. doi: 10.1159/000218334. Epub 2009 Jun 29.
Inhibitor of growth (ING) 4 is a member of the ING family proteins. It has been shown to play an important role in cell cycle, transcription and oncogenesis, but the molecular mechanism of ING4 on tumor growth inhibition has not yet been elucidated. The goal of this study is to investigate the inhibitory effects of ING4 on gliomas and its mechanism by transduction of ING4 cDNA into glioma U87MG.
The effect and mechanisms of ING4 on proliferation and apoptosis of U87MG were evaluated in vitro by MTT assay, flow-cytometric analysis, TUNEL assay, Western blot analysis and animal experiments.
The level of ING4 was markedly reduced in glioma tissues, and the extent of reduction correlated with the progression from lower to higher grades of tumors. It was observed that U87MG with exogenous ING4 gene presented with growth suppression, apoptosis enhancement and the deregulation of cell cycle- or apoptosis-regulating proteins.
ING4 has a potential role on the growth suppression and apoptosis enhancement in gliomas U87MG via the activation of mitochondrial-induced apoptotic pathway and the hindrance of the cell cycle progression. The low expression and dysfunction of ING4 might be correlated with the tumorigenesis and progression of gliomas.
生长抑制因子(ING)4是ING家族蛋白成员之一。已证明其在细胞周期、转录及肿瘤发生过程中发挥重要作用,但ING4抑制肿瘤生长的分子机制尚未阐明。本研究旨在通过将ING4 cDNA转导入胶质瘤U87MG细胞,探讨ING4对胶质瘤的抑制作用及其机制。
采用MTT法、流式细胞术分析、TUNEL检测、蛋白质免疫印迹分析及动物实验等方法,在体外评估ING4对U87MG细胞增殖和凋亡的影响及机制。
胶质瘤组织中ING4水平显著降低,且降低程度与肿瘤分级从低到高的进展相关。观察到携带外源性ING4基因的U87MG细胞出现生长抑制、凋亡增强以及细胞周期或凋亡调节蛋白失调。
ING4可能通过激活线粒体诱导的凋亡途径及阻碍细胞周期进程,对胶质瘤U87MG细胞发挥生长抑制和凋亡增强作用。ING4的低表达及功能异常可能与胶质瘤的发生及进展相关。