基质金属蛋白酶基因表达可能是胃癌细胞系中氧化应激的靶点。
Matrix metalloproteinase gene expressions might be oxidative stress targets in gastric cancer cell lines.
机构信息
Department of Genetics and Bioengineering, Faculty of Engineering, Fatih University, Istanbul 34500, Turkey; ; Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Uskudar University, Istanbul 34662, Turkey;
出版信息
Chin J Cancer Res. 2013 Jun;25(3):322-33. doi: 10.3978/j.issn.1000-9604.2013.06.05.
OBJECTIVE
Oxidative stress is linked to increased risk of gastric cancer and matrix metalloproteinases (MMPs) are important in the invasion and metastasis of gastric cancer. We aimed to analyze the effect of the accumulation of oxidative stress in the gastric cancer MKN-45 and 23132/87 cells following hydrogen peroxide (H2O2) exposure on the expression patterns of MMP-1, MMP-3, MMP-7, MMP-9, MMP-10, MMP-11, MMP-12, MMP-14, MMP-15, MMP-17, MMP-23, MMP-28, and β-catenin genes.
METHODS
The mRNA transcripts in the cells were determined by RT-PCR. Following H2O2 exposure, oxidative stress in the viable cells was analyzed by 2',7'-dichlorofluorescein diacetate (DCFH-DA). Caffeic acid phenethyl ester (CAPE) was used to eliminate oxidative stress and the consequence of H2O2 exposure and its removal on the expressions of the genes were evaluated by quantitative real-time PCR.
RESULTS
The expressions of MMP-1, MMP-7, MMP-14, MMP-15, MMP-17 and β-catenin in MKN-45 cells and only the expression of MMP-15 in 23132/87 cells were increased. Removal of the oxidative stress resulted in decrease in the expressions of MMP genes of which the expressions were increased after H2O2 exposure. β-catenin, a transcription factor for many genes including MMPs, also displayed decreased levels of expression in both of the cell lines following CAPE treatment.
CONCLUSIONS
Our data suggest that there is a remarkable link between the accumulation of oxidative stress and the increased expressions of MMP genes in the gastric cancer cells and MMPs should be considered as potential targets of therapy in gastric cancers due to its continuous exposure to oxidative stress.
目的
氧化应激与胃癌风险增加有关，基质金属蛋白酶（MMPs）在胃癌的侵袭和转移中起着重要作用。本研究旨在分析胃癌 MKN-45 和 23132/87 细胞在过氧化氢（H2O2）暴露后，氧化应激积累对 MMP-1、MMP-3、MMP-7、MMP-9、MMP-10、MMP-11、MMP-12、MMP-14、MMP-15、MMP-17、MMP-23、MMP-28 和 β-连环蛋白基因表达模式的影响。
方法
采用 RT-PCR 法检测细胞中的 mRNA 转录本。用 2'，7'-二氯荧光素二乙酸酯（DCFH-DA）分析活细胞中的氧化应激。用咖啡酸苯乙酯（CAPE）消除氧化应激，并通过定量实时 PCR 评估 H2O2 暴露及其去除对基因表达的影响。
结果
MKN-45 细胞中 MMP-1、MMP-7、MMP-14、MMP-15、MMP-17 和 β-连环蛋白的表达增加，23132/87 细胞中仅 MMP-15 的表达增加。消除氧化应激导致 H2O2 暴露后表达增加的 MMP 基因表达减少。β-连环蛋白是包括 MMP 在内的许多基因的转录因子，在 CAPE 处理后两种细胞系中的表达水平也降低。
结论
我们的数据表明，胃癌细胞中氧化应激的积累与 MMP 基因表达的增加之间存在显著联系，由于 MMP 持续暴露于氧化应激，因此 MMP 应被视为胃癌治疗的潜在靶点。
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