Effect of Timolol Maleate on the Expression of Vascular Endothelial Growth Factor Induced Signal Transduction Pathway in Human Umbilical Vein Endothelial Cells

doi:10.3969/j.issn.1005-4979.2018.04.005

Abstract

Abstract: Objective: The aim of this study was to investigate whether the expression of the vasculogenic signaling pathway in human umbilical vein endothelial cells (HUVEC)could be specifically targeted and inhibited by timolol maleate. Methods: RT-PCR and Western blot were used to detect the expression of Auto-ja Kuljetusalan Ty?觟ntekijliitto （Akt）, Extracellular regulated protein kinases （ERK）, focal adhesion kinase（FAK） and mammalian target of rapamycin （mTOR）, and SPSS17.0 statistical package was used to analyze the data. Results: RT-PCR detection showed that timolol maleate significantly inhibited the expression of vascular endothelial growth factor（VEGF） induced ERK, Akt, mTOR and FAK mRNA in a dose-dependent manner. Western blot results showed that timolol maleate significantly inhibited the regulation of p-ERK, p-Akt, and phosphorylation of VEGF in a dose-dependent manner. Conclusion: Timolol maleate can inhibit the expression of ERK, Akt, mTOR, FAK signaling pathway to inhibit the proliferation of vascular endothelial cells and promote cell apoptosis, so as to achieve the purpose of treating infantile hemangioma.

Key words: timolol maleate, signal transduction pathway, VEGF induction

摘要： 目的：研究马来酸噻吗洛尔在人脐静脉内皮细胞（HUVEC）中血管生成信号传导通路的表达，以探讨这些药物作为治疗婴幼儿血管瘤的作用机制。方法：采用RT-PCR和Western blot检测蛋白激酶B（Akt）、细胞外调节蛋白激酶（ERK）、局部黏着斑激酶（FAK）和哺乳动物雷帕霉素靶蛋白（mTOR）的表达。应用SPSS17.0统计包进行数据分析。结果：RT-PCR检测发现，马来酸噻吗洛尔以剂量依赖的方式明显抑制血管内皮生长因子（vascular endothelial growth factor，VEGF）诱导的ERK、Akt、mTOR及FAK的mRNA表达；Western blot结果显示：马来酸噻吗洛尔以剂量依赖的方式明显抑制VEGF对磷酸化的细胞外调节蛋白激酶（p-ERK）、磷酸化蛋白激酶B（p-Akt）、磷酸化的哺乳动物雷帕霉素靶蛋白（p-mTOR）的调控。结论：马来酸噻吗洛尔可以通过抑制ERK、Akt、mTOR、FAK信号通路的表达，抑制血管瘤内皮细胞增殖和促进细胞凋亡，从而达到治疗婴幼儿血管瘤的目的。

关键词: 马来酸噻吗洛尔, 信号通路, 血管生长因子诱导

CLC Number:

R856.78

SUI Qi-jia, XIN Xiao-tao. Effect of Timolol Maleate on the Expression of Vascular Endothelial Growth Factor Induced Signal Transduction Pathway in Human Umbilical Vein Endothelial Cells[J]. 《Journal of Oral and Maxillofacial Surgery》, doi: 10.3969/j.issn.1005-4979.2018.04.005.

隋琦佳，莘晓陶. 马来酸噻吗洛尔对人脐静脉内皮细胞的VEGF传导通路表达的影响[J]. 《口腔颌面外科杂志》, doi: 10.3969/j.issn.1005-4979.2018.04.005.

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URL: https://journal06.magtech.org.cn/Jweb_joms/EN/10.3969/j.issn.1005-4979.2018.04.005

https://journal06.magtech.org.cn/Jweb_joms/EN/Y2018/V28/I4/204

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