Miao YiMing, Cui LiuQing, Chen ZhiQiang, Zhang Lu
a College of Bioengineering, Henan University of Technology , Zhengzhou , China.
Pharm Biol. 2016;54(4):660-6. doi: 10.3109/13880209.2015.1071414. Epub 2015 Oct 1.
trans-3,4,5,4'-Tetramethoxystilbene (DMU-212), an derivative of resveratrol, shows strong antiproliferative activities against many cancer cells. In our previous study, we demonstrated that DMU-212 possesses potent proapoptosis and antiangiogenesis effects on vascular endothelial cells (VECs), which made it a promising agent for the treatment of angiogenesis-related diseases.
We studied the gene expression profile of DMU-212-treated VECs to gain further insight into the mechanisms by which DMU-212 exerts its potent pro-apoptosis and antiangiogenesis effects.
The potential changes in the gene expression of VECs incubated with DMU-212 were identified and analyzed using the Affymetrix HG-U133 Plus 1.0 array. In addition, the gene expression profile was validated by quantitative real-time PCR (qRT-PCR) analysis for seven of those altered genes.
DMU-212 was found to regulate a diverse range of genes, including cytokines (IL8, selectin E, MPZL2, EGR1, CCL20, ITGB8, CXCL1, VCAM1, KITLG, and AREG), transport proteins (TRPC4, SLC41A2, SLC17A5, and CREB5), metabolism (CYP1B1, CYP1A1, PDK4, CSNK1G1, MVK, TCEB3C, and CDKN3), enzymes (RAB23, SPHK1, CHSY3, PLAU, PLA2G4C, and MMP10), and genes involved in signal transduction (TMEM217, DUSP8, and SPRY4), chromosome organization (HIST1H2BH and GEM), cell migration and angiogenesis (ERRFI1, HBEGF, and NEDD9), and apoptosis (TNFSF15, TNFRSF9, CD274, BCL2L11, BIRC3, TNFAIP3, and TIFA), as well as other genes with unknown function (PGM5P2, SNORD1142, LOC151760, KRTAP5-2, C1orf110, SNORA14A, MIR31, C2CD4B, SCARNA4, C2orf66, SC4MOL, LOC644714, and LOC283392). This is the first application of microarray technique to investigate and analyze the profile of genes regulated by DMU-212 in VECs. Our results lead to an increased understanding of the signaling pathways involved in DMU-212-induced apoptosis and antiangiogenesis.
反式-3,4,5,4'-四甲氧基二苯乙烯（DMU-212）是白藜芦醇的衍生物，对多种癌细胞具有强大的抗增殖活性。在我们之前的研究中，我们证明DMU-212对血管内皮细胞（VECs）具有强大的促凋亡和抗血管生成作用，这使其成为治疗血管生成相关疾病的有前景的药物。
我们研究了经DMU-212处理的VECs的基因表达谱，以进一步深入了解DMU-212发挥其强大的促凋亡和抗血管生成作用的机制。
使用Affymetrix HG-U133 Plus 1.0芯片鉴定并分析与DMU-212孵育的VECs基因表达的潜在变化。此外，通过定量实时PCR（qRT-PCR）分析对其中7个改变的基因进行基因表达谱验证。
发现DMU-212可调节多种基因，包括细胞因子（IL8、选择素E、MPZL2、EGR1、CCL20、ITGB8、CXCL1、VCAM1、KITLG和AREG）、转运蛋白（TRPC4、SLC41A2、SLC17A5和CREB5）、代谢（CYP1B1、CYP1A1、PDK4、CSNK1G1、MVK、TCEB3C和CDKN3）、酶（RAB23、SPHK1、CHSY3、PLAU、PLA2G4C和MMP10）以及参与信号转导（TMEM217、DUSP8和SPRY4）、染色体组织（HIST1H2BH和GEM）、细胞迁移和血管生成（ERRFI1、HBEGF和NEDD9）、凋亡（TNFSF15、TNFRSF9、CD274、BCL2L11、BIRC3、TNFAIP3和TIFA）的基因，以及其他功能未知的基因（PGM5P2、SNORDl14-2、LOC151760、KRTAP5-2、C1orf110、SNORA14A、MIR31、C2CD4B、SCARNA4、C2orf66、SC4MOL、LOC644714和LOC283392）。这是首次应用微阵列技术研究和分析DMU-212在VECs中调节的基因谱。我们的结果有助于增加对DMU-212诱导的凋亡和抗血管生成所涉及的信号通路的理解。
