CAJ | 학술논문

目的探讨胶质瘤中Hedgehog/Gli1信号通路的活化与肿瘤微血管新生之间的关系.方法 54例手术切除的胶质瘤肿瘤标本,免疫组织化学检测胶质瘤组织中Gli与肿瘤微血管密度(MVD)表达的关系；运用Western blot法及定量聚合酶链反应(PCR)检测U87、SHG44、U251及A172胶质瘤细胞中Gli1与血管内皮生长因子(VEGF)在蛋白及mRNA水平的表达；U87、SHG44中通过环巴胺(Cyclopamine)处理胶质瘤细胞束抑制Hedgehog/Gli1信号通路,观察这一信号通路活性下降后对胶质瘤中VEGF表达的影响.结果随着Hedgehog/Gli1信号通路中Gli1表达数量的增加,MVD也相应地升高；在胶质瘤细胞株U87、SHG44、U251及A172中,U87及SHG44中Hedgehog/Gli1信号通路的活化程度较高,同时VEGF基因及蛋白的表达水平较高；通过Cyclopamine抑制这一信号通路可明显下调胶质瘤细胞中VEGF的表达,其中5μmol/L Cyclopamine组VEGF的表达分别下降至(33.3±3.3)％(U87细胞),(27.1±3.0)％(SHG44细胞)；10 μmol/L组VEGF的表达分别下降至(14.7±29)％( U87),(16.3±2.4)％(SHG44).结论部分胶质瘤中存在Hedgehog/Gli1信号通路活化,而且这一信号通路活化程度与胶质瘤的血管新生密切相关.
목적 탐토효질류중Hedgehog/Gli1신호통로적활화여종류미혈관신생지간적관계.방법 54례수술절제적효질류종류표본,면역조직화학검측효질류조직중Gli여종류미혈관밀도(MVD)표체적관계；운용Western blot법급정량취합매련반응(PCR)검측U87、SHG44、U251급A172효질류세포중Gli1여혈관내피생장인자(VEGF)재단백급mRNA수평적표체；U87、SHG44중통과배파알(Cyclopamine)처리효질류세포속억제Hedgehog/Gli1신호통로,관찰저일신호통로활성하강후대효질류중VEGF표체적영향.결과 수착Hedgehog/Gli1신호통로중Gli1표체수량적증가,MVD야상응지승고；재효질류세포주U87、SHG44、U251급A172중,U87급SHG44중Hedgehog/Gli1신호통로적활화정도교고,동시VEGF기인급단백적표체수평교고；통과Cyclopamine억제저일신호통로가명현하조효질류세포중VEGF적표체,기중5μmol/L Cyclopamine조VEGF적표체분별하강지(33.3±3.3)％(U87세포),(27.1±3.0)％(SHG44세포)；10 μmol/L조VEGF적표체분별하강지(14.7±29)％( U87),(16.3±2.4)％(SHG44).결론 부분효질류중존재Hedgehog/Gli1신호통로활화,이차저일신호통로활화정도여효질류적혈관신생밀절상관.
Objective To investigate the correlation between Hedgehog/Gli signaling pathway and tumor angiogenesis in glioma,and analyze the correlation between vascular endothelial growth factor (VEGF) expression and Hedgehog/Gli signaling pathway regulation of glioma.Methods In 54 cases of resected specimens from patients with glioma after surgery,immunohistochemistry was used to detect the expression of CD34 and Gli1 proteins to explore the relationship between the Hedgehog/Gli1 pathway and tumour angiogenesis.Extracellular inhibiting ligand Cyclopamine was used to repress the Hedgehog/Gli1 pathway in U87 and SHG4 cells in order to explore whether repression of this pathway could upregulate or downregulate the expression of VEGF.Results Gli1 expression was positively related with microvessel density (MVD) in glioma.Overactivation of the Hedgehog/Gli1 pathway effectively upregulated the VEGF expression,while repression of the Hedgehog/Gli1 pathway activity promoted downregulation of the VEGF expression.Conclusion Status of the Hedgehog/Gli1 pathway activated is correlated with angiogenesis in gliomas.The Hedgehog/Gli1 pathway can effectively regulate the expression of VEGF.