过氧化氢通过DLC1/RhoA信号通路抑制癌细胞增殖并介导迁移抑制。
H2O2 inhibits proliferation and mediates suppression of migration via DLC1/RhoA signaling in cancer cells.
作者信息
Ma Long, Zhu Wen-Zhen, Liu Ting-Ting, Fu Hui-Ling, Liu Zhao-Jun, Yang Bing-Wu, Song Tai-Yu, Li Guo-Rong
机构信息
Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, China E-mail :
出版信息
Asian Pac J Cancer Prev. 2015;16(4):1637-42. doi: 10.7314/apjcp.2015.16.4.1637.
BACKGROUND
RhoGTPase-activating proteins (RhoGAPs) regulate RhoGTPases in cells, but whether individual reactive oxygen species (ROS) regulate RhoGAPs is unknown. Our previous published papers have shown that deleted in liver cancer 1 (DLC1) inhibits cancer cell migration by its RhoGAP activity. The present study was designed to explore the role of H2O2 in regulation of DLC1.
MATERIALS AND METHODS
We treated cells with H2O2 for 24h and phenotypic changes were analyzed by MTT, RT-PCR, Western blotting, immunofluorescence staining and wound healing assays.
RESULTS
H2O2 downregulated cyclin D1 and cyclin E to inhibit proliferation, and upregulated BAX to induce apoptosis in MCF-7 cells. Compared with non-tumorigenic cells, H2O2 increased expression of DLC1 and reduced activity of RhoA in cancer cells. Stress fiber production and migration were also suppressed by H2O2 in MDA-MB-231 cells.
CONCLUSIONS
Our study suggests that H2O2 inhibits proliferation through modulation of cell cycle and apoptosis-related genes, and inhibits migration by decreasing stress fibers via DLC1/RhoA signaling.
背景
RhoGTP酶激活蛋白（RhoGAPs）在细胞中调节RhoGTP酶，但单个活性氧（ROS）是否调节RhoGAPs尚不清楚。我们之前发表的论文表明，肝癌缺失1（DLC1）通过其RhoGAP活性抑制癌细胞迁移。本研究旨在探讨H2O2在DLC1调节中的作用。
材料与方法
我们用H2O2处理细胞24小时，并通过MTT、RT-PCR、蛋白质免疫印迹、免疫荧光染色和伤口愈合试验分析表型变化。
结果
H2O2下调细胞周期蛋白D1和细胞周期蛋白E以抑制增殖，并上调BAX以诱导MCF-7细胞凋亡。与非致瘤细胞相比，H2O2增加了癌细胞中DLC1的表达并降低了RhoA的活性。H2O2还抑制了MDA-MB-231细胞中的应力纤维生成和迁移。
结论
我们的研究表明，H2O2通过调节细胞周期和凋亡相关基因来抑制增殖，并通过DLC1/RhoA信号传导减少应力纤维来抑制迁移。
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