热休克蛋白90-细胞外信号调节激酶-血管内皮生长因子通路在肠癌所致血管内皮细胞迁移和管状生成中的作用及机制  

Heat shock protein 90-extracellular regulated protein kinases-vascular endothelial growth factor signaling induces vascular cells migration and angiogenesis in colorectal cancer

作　　者：周建平[1] 王维民[2] 邓建良[2] 周苏君[1] 周炎[2] 戴小军 吴露露[1] 郭治源[1] 史建能 史俊[1] 

机构地区：[1]江苏大学附属宜兴医院胃肠外科,江苏宜兴214200 [2]江苏大学附属宜兴医院肿瘤科,江苏宜兴214200 [3]扬州市中医院肿瘤科

出　　处：《中华实验外科杂志》2014年第10期2164-2166,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金青年资助项目（81001589）;江苏大学医学临床科技发展基金资助项目（JLY2010044）

摘　　要：目的 探讨热休克蛋白90（HSP90）-细胞外信号调节激酶（ERK）-血管内皮生长因子（VEGF）信号通路在肠癌所致血管内皮细胞迁移和管状生成中作用及可能机制.方法 改变肠癌细胞HCT116中HSP90的表达水平,观察对下游分子ERK磷酸化激活和VEGF表达的影响;肠癌细胞条件培养上清刺激人脐静脉血管内皮（HUVECs）细胞,观察HUVECs细胞在该培养液中迁移和管状生成的能力;同时采用ERK抑制剂U0126和人重组VEGF蛋白,观察可否部分逆转因肠癌细胞中HSP90表达改变对血管细胞活性的影响.结果 TNM分期Ⅱ、Ⅲ、Ⅳ的肠癌患者癌组织中VEGF表达量高于对应癌旁组织.高表达HSP90增加了VEGF介导的HUVECs细胞迁移和血管生成的能力.U0126处理肠癌细胞后,抑制ERK的激活,可部分逆转因HSP90表达增加而引起的肠癌细胞中VEGF表达量的增加.结论 HSP90-ERK-VEGF通路在肠癌所致血管生成中发挥中重要作用.Objective To explore whether heat shock protein 90 （HSP90）-extracellular regulated protein kinases （ERK）-vascular endothelial growth factor （VEGF） signaling could induce vascular cells migration and angiogenesis in colorectal cancer and underlying mechanisms.Methods The expression of VEGF in colorectal cancer and adjacent normal tissue was detected by Western blotting.Wound healing and tube formation asssay were applied to evaluate the angiogenesis ability of human umbilical vein endothelial cells （HUVECS） in the conditional medium collected from colorectal cancer cell line （HCT116）.Results VEGF expression level was higher in fresh colorectal cancer tissues compared with adjacent normal tissues in the patients of stage Ⅱ,Ⅲ,Ⅳ.HSP90 activates phosphorylation of ERK to induce the expression of secretory VEGF in HCT116,thus enhancing the migration and tube formation ability of HUVECS in the conditional medium.Enhanced angiogenesis activity was partially reversed by U0126 treatment.Conclusion HSP90-ERK-VEGF pathway plays an important role in angiogenesis of colorectal cancer.

关 键 词：结直肠癌 热休克蛋白90 细胞外信号调节激酶 血管内皮生长因子 血管生成 

分 类 号：R735.34[医药卫生—肿瘤]