重组人类肝细胞生长因子对胶质瘤细胞增殖及VEGF表达的影响  

The effects of recombinant human hepatocyte growth factor on proliferation and VEGF expression of glioma cells

作　　者：李志强[1] 楚胜华[1] 袁先厚[1] 江普查[1] 文志华[1] 

机构地区：[1]武汉大学中南医院神经外科,湖北武汉430071

出　　处：《中华神经外科疾病研究杂志》2006年第5期422-425,共4页Chinese Journal of Neurosurgical Disease Research

基　　金：湖北省卫生厅科研基金资助项目(JX1B019)

摘　　要：目的探讨重组人类肝细胞生长因子(rhHGF)对胶质瘤细胞增殖及血管内皮生长因子(VEGF)表达的影响。方法用5、10、20、30μg/L不同浓度的rhHGF作用于体外培养的U251胶质瘤细胞并设立空白对照组,甲基噻唑基四唑(MTT)法检测细胞增殖;免疫组化及Westernblot检测增殖细胞核抗原(PCNA)和VEGF表达。结果与对照组相比,rhHGF明显促进U251细胞的增殖和生长,其作用呈时间效应关系和一定浓度范围内的剂量效应关系(P<0.05)。Westernblot及免疫组化检测显示,20μg/LrhHGF作用后U251细胞PCNA和VEGF表达上升,呈时间依赖性(P<0.05);细胞外调节蛋白激酶(ERK)抑制剂PD98059呈剂量依赖性抑制rhHGF诱导的PCNA和VEGF表达增加。结论rhHGF可能通过ERK信号途径促进胶质瘤细胞增殖和VEGF表达,从而影响胶质瘤的生长和血管发生。Objective To study the effects of recombinant human hepatocyte growth factor （rhHGF） on proliferation and vascular endothelial growth factor （ VEGF ） expression of glioma cells. Methods In vitro cultured human U251 glioma cells were incubated with 0, 5, 10, 20 and 30 μg/L rhHGF respectively. Methyl thiazolyl tetrazolium （MTI＇） assay was used to evaluate cell growth. Expression of proliferating cell nuclear antigen （PCNA）, VEGF and extracellular signal-regulated kinase （ERK） proteins were determined by immunohistochemistry and Western blot. Results Comparing to the control group, rhHGF made a significant increase in the growth and proliferation of U251 cells in a time dependent manner and in a dose dependent manner from 0 to 20μg/L （ P 〈 0. 05 ）. After treatment with 20 μg/L rhHGF, the expression of PCNA and VEGF increased significantly in a time dependent manner （ P 〈0. 05 ）. PD98059, an extracellular signal-regulated kinase （ERK） inhibitor, could significantly inhibit the rhHGF-induced increase of PCNA and VEGF in a dose dependent manner. Conclusion By activating ERK signal pathway, rhHGF may have effects on glioma angiogenesis through up-regulating VEGF expression and on cell proliferation.

关 键 词：胶质瘤 肝细胞生长因子 细胞增殖 血管发生 细胞外调节激酶 

分 类 号：R739.41[医药卫生—肿瘤]