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DZNep抑制Hif-1α和Wnt信号分子,以减弱BGC-823胃癌细胞的增殖和侵袭。

DZNep inhibits Hif-1α and Wnt signalling molecules to attenuate the proliferation and invasion of BGC-823 gastric cancer cells.

作者信息

Huang Rui, Jin Xiu, Gao Yongying, Yuan Hongmei, Wang Fei, Cao Xiangmei

机构信息

Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.

Department of Pathology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.

出版信息

Oncol Lett. 2019 Oct;18(4):4308-4316. doi: 10.3892/ol.2019.10769. Epub 2019 Aug 22.

Abstract

3-deazaneplanocin A (DZNep) is a histone methyltransferase inhibitor, which may cause the reactivation of silenced tumor suppressor genes in tumors to inhibit the development, metastasis and dissemination of tumor cells. However, the effects and mechanisms of its application in gastric cancer remain unclear. The present study revealed an inhibitory function of DZNep in BGC-823 cells. The cell colony, Cell Counting Kit-8 (CCK8), wound healing, Transwell and flow cytometry assays were performed, and the results demonstrated that DZNep could inhibit the proliferation, apoptosis and invasion of BGC-823 cells, and promote their apoptosis. The effects of intervention in BDC-823 cells with DZNep on the RNA and protein expression levels of hypoxia-inducible factor (Hif-1α) and Wnt/β-catenin signalling molecules were further examined using reverse transcription-quantitative PCR and western blot analysis. The results demonstrated that different concentrations of DZNep could inhibit the expression of enhancer of zeste homolog 2 (EZH2) protein, decrease the RNA and protein expression levels of Hif-1α, total β-catenin and phosphorylated-β-catenin and increase the expression levels of non-phosphorylated-β-catenin to different degrees. The results of the present study suggests that DZNep inhibits BGC-823 gastric cancer cells via the inhibition of EZH2, Hif-1α and Wnt/β-catenin signalling molecules. These results provide theoretical basis for the application of DZNep in clinical trials.

摘要

3-去氮杂氮胞苷(DZNep)是一种组蛋白甲基转移酶抑制剂,它可能会使肿瘤中沉默的抑癌基因重新激活,从而抑制肿瘤细胞的生长、转移和扩散。然而,其在胃癌中的作用及机制仍不清楚。本研究揭示了DZNep对BGC-823细胞具有抑制作用。进行了细胞集落、细胞计数试剂盒-8(CCK8)、伤口愈合、Transwell和流式细胞术检测,结果表明DZNep可抑制BGC-823细胞的增殖、侵袭并促进其凋亡。进一步采用逆转录定量PCR和蛋白质印迹分析检测了用DZNep干预BDC-823细胞对缺氧诱导因子(Hif-1α)和Wnt/β-连环蛋白信号分子的RNA和蛋白质表达水平的影响。结果表明,不同浓度的DZNep均可抑制zeste同源物2(EZH2)蛋白的表达,不同程度地降低Hif-1α、总β-连环蛋白和磷酸化-β-连环蛋白的RNA和蛋白质表达水平,并提高非磷酸化-β-连环蛋白的表达水平。本研究结果提示,DZNep通过抑制EZH2、Hif-1α和Wnt/β-连环蛋白信号分子来抑制BGC-823胃癌细胞。这些结果为DZNep在临床试验中的应用提供了理论依据。

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