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血管内皮细胞通过Notch信号通路对胶质瘤细胞侵袭性生长的影响[J]. 肿瘤防治研究, 2015, 42(07): 652-656. DOI: 10.3971/j.issn.1000-8578.2015.07.003
引用本文: 血管内皮细胞通过Notch信号通路对胶质瘤细胞侵袭性生长的影响[J]. 肿瘤防治研究, 2015, 42(07): 652-656. DOI: 10.3971/j.issn.1000-8578.2015.07.003
Effects of Vascular Endothelial Cells on Invasion of Glioma Cells via Notch Signal Pathway[J]. Cancer Research on Prevention and Treatment, 2015, 42(07): 652-656. DOI: 10.3971/j.issn.1000-8578.2015.07.003
Citation: Effects of Vascular Endothelial Cells on Invasion of Glioma Cells via Notch Signal Pathway[J]. Cancer Research on Prevention and Treatment, 2015, 42(07): 652-656. DOI: 10.3971/j.issn.1000-8578.2015.07.003

血管内皮细胞通过Notch信号通路对胶质瘤细胞侵袭性生长的影响

Effects of Vascular Endothelial Cells on Invasion of Glioma Cells via Notch Signal Pathway

  • 摘要: 目的 探讨血管内皮细胞对胶质瘤细胞侵袭力的影响及其与Notch信号通路之间的关系。 方法 在体外采用Transwell共培养系统将人脐静脉内皮细胞(human umbilical vein endothelial cells, HUVEC)和U87胶质瘤细胞进行间接共培养;抑制剂DAPT(N-N-(3,5-di-fluorophenacetyl)-L-alanyl- S-phenylglycinet-butylester)抑制Notch信号通路;Transwell小室快速检测各组U87细胞的侵袭力;Real-time PCR检测各组U87细胞中Notch1、Notch2、Hes1、Delta样配体4(Dll4)、Cathepsins B、MMP-9、MMP-2 mRNA的表达情况;Western blot检测各组U87细胞中MMP-9、MMP-2蛋白、Cathepsins B的表达情况。结果 共培养组较单纯组U87细胞生长旺盛,DAPT处理后生长受抑制;共培养组穿过Matrigel膜的U87细胞数目明显多于单纯组,DAPT处理组较共培养组穿膜细胞数目减少。共培养组U87细胞的Notch1、Notch2、Hes1、Dll4、Cathepsins B、MMP-9 mRNA的表达及各组U87胶质瘤细胞中MMP-9、Cathepsins B蛋白的表达水平明显升高,DAPT处理组较共培养组相关的mRNA和蛋白水平降低。结论 血管内皮细胞可以通过Notch信号通路增强U87胶质瘤细胞的侵袭力,DAPT抑制Notch信号通路可以降低血管内皮细胞对U87胶质瘤细胞侵袭力的增强效果,Notch信号通路在血管内皮细胞对U87胶质瘤细胞的侵袭力的增强过程中起重要的调控作用。

     

    Abstract: Objective To investigate the effects of vascular endothelial cells on the invasion properties of glioma cells and their relationships with Notch signal pathway. Methods We co-cultured human umbilical vein endothelial cells(HUVEC) and U87 glioma cells by Transwell in vitro, inhibited the Notch signal pathway using DAPT, and then analyzed the invasiveness of U87 cells of each group in matrigel matrix, in vitro. Realtime PCR was conducted to detect the mRNA expressions of Notch1, Notch2, Hes1, Dll4, Cathepsins B, MMP-9, MMP-2. The protein expressions of Cathepsins B, MMP-9, MMP-2 were detected by Western blot. Results The U87 cells grew much thrived when co-cultured with HUVEC, but the growth was restrained when treated with DAPT. The co-cultured U87 showed more aggressive than single U87 cells and U87 cells dealt with DAPT. The mRNA expressions of Notch1, Notch2, Hes1, Dll4, Cathepsins B, MMP-9 and the protein expressions of Cathepsins B, MMP-9 of U87 cells co-cultured with HUVEC were increased obviously, but then they were decreased when treated with DAPT. Conclusion The invasion of U87 cells might be promoted by interactions of glioma cells and endothelial cells, which have a close relation with Notch signal pathway, and DAPT could weaken the promotion effects by inhibiting Notch signal pathway.

     

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