摘要
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Westernblot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）处理胶质瘤细胞来抑制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5umol／LCyclopamine组VEGF的表达分别下降至（33．3±3．3）％（U87细胞），（27．1±3．0）％（SHG44细胞）；10umol／L组VEGF的表达分别下降至（14．7±2．9）％（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。
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 reseeted specimens from patients with glioma after surgery, immunohistochemistry was used to detect the expression of CD34 and Glil proteins to explore the relationship between the Hedgehog/Glil pathway and tumour angiogenesis. Extracellular inhibiting ligand Cyclopamine was used to repress the Hedgehog/Glil pathway in U87 and SHG4 cells in order to explore whether repression of this pathway could upregulate or downregnlate the expression of VEGF. Results Glil expression was positively related with microvessel density （MVD） in glioma. Overactivation of the Hedgehog/Glil pathway effectively upregulated the VEGF expression, while repression of the Hedgehog/Glil pathway activity promoted downregulation of the VEGF expression. Conclusion Status of the Hedgehog/Glil pathway activated is correlated with angiogenesis in gliomas. The Hedgehog/Glil pathway can effectively regulate the expression of VEGF.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2012年第5期903-906,共4页
Chinese Journal of Experimental Surgery
基金
江苏省高校自然科学基金资助项目（09KJB320011）
江苏省科教兴卫工程（临床医学中心重点学科）开放课题项目（KF200970）
江苏省南通市社会发展科技计划项目（S2009028）
关键词
胶质瘤
血管内皮生长因子
信号通路
Glioma
Vascular endothelial growth factor
Signaling pathway
