Expression of NOTCH4 affects vasculogenic mimicry formation in hepatocellular carcinoma
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摘要:
目的研究NOTCH4基因表达对肝细胞癌血管生成拟态(VM)形成的影响。方法收集2010年-2014年间85例病理确诊为肝细胞癌的组织标本,免疫组织化学染色及PAS/CD31双染检测NOTCH4表达与VM的相关性;在体外三维细胞培养体系中靶向抑制肝癌细胞NOTCH4的表达,观察其对VM管状结构形成的影响。采用Mann-Whitney U秩和检验和单因素方差分析处理数据。结果 VM阳性的组织标本中NOTCH4高表达(P=0.019);siRNA组相对于阴性对照组及空白对照组,NOTCH4基因的mRNA表达(P值分别为0.007、0.003)及蛋白表达(P值均为0.000)均明显下调,差异具有统计学意义;靶向抑制NOTCH4的表达影响肝癌细胞在三维细胞培养体系中VM管状结构的形成。结论 NOTCH4基因表达影响肝细胞癌中VM的形成,可能成为肝细胞癌抗血管生成治疗的新靶点。
Abstract:Objective To investigate the effect of NOTCH4 expression on vasculogenic mimicry( VM) formation in hepatocellular carcinoma( HCC). Methods Tumor tissues were collected from 85 patients diagnosed with HCC. The relationship between NOTCH4 expression and VM was examined using immunohistochemical staining and PAS / CD31 double staining. The influence of siRNA- mediated NOTCH4 silencing on VM network formation in HCC was observed in the 3D cell culture system in vitro. Experimental data were assessed with Mann-Whitney U test and one- way analysis of variance. Results NOTCH4 had significantly higher expression in VM- positive HCC tissues than in VM- negative HCC tissues( P = 0. 019). In siRNA- treated cells,NOTCH4 mRNA and protein expression was significantly down- regulated compared with those in mock- treated cells( P = 0. 007; P = 0. 003) and untreated cells( P = 0. 000; P = 0. 000). VM network formation was impaired by inhibition of NOTCH4 expression in the 3D cell culture system. Conclusion NOTCH4 plays an important role in VM formation in HCC and may provide a novel molecular target for anti- angiogenesis therapy for HCC.
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Key words:
- carcinoma,hepatocellular /
- vasculogenic mimicry /
- genes,tumor suppressor
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