中华实验外科杂志
中華實驗外科雜誌
중화실험외과잡지
CHINESE JOURNAL OF EXPERIMENTAL SURGERY
2014年
10期
2164-2166
,共3页
周建平%王维民%邓建良%周苏君%周炎%戴小军%吴露露%郭治源%史建能
週建平%王維民%鄧建良%週囌君%週炎%戴小軍%吳露露%郭治源%史建能
주건평%왕유민%산건량%주소군%주염%대소군%오로로%곽치원%사건능
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
結直腸癌%熱休剋蛋白90%細胞外信號調節激酶%血管內皮生長因子%血管生成
결직장암%열휴극단백90%세포외신호조절격매%혈관내피생장인자%혈관생성
Colorectal cancer%Heat shock protein 90%Extracellular regulated protein kinases%Vascular endothelial growth factor%Angiogenesis
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.
目的 探討熱休剋蛋白90(HSP90)-細胞外信號調節激酶(ERK)-血管內皮生長因子(VEGF)信號通路在腸癌所緻血管內皮細胞遷移和管狀生成中作用及可能機製.方法 改變腸癌細胞HCT116中HSP90的錶達水平,觀察對下遊分子ERK燐痠化激活和VEGF錶達的影響;腸癌細胞條件培養上清刺激人臍靜脈血管內皮(HUVECs)細胞,觀察HUVECs細胞在該培養液中遷移和管狀生成的能力;同時採用ERK抑製劑U0126和人重組VEGF蛋白,觀察可否部分逆轉因腸癌細胞中HSP90錶達改變對血管細胞活性的影響.結果 TNM分期Ⅱ、Ⅲ、Ⅳ的腸癌患者癌組織中VEGF錶達量高于對應癌徬組織.高錶達HSP90增加瞭VEGF介導的HUVECs細胞遷移和血管生成的能力.U0126處理腸癌細胞後,抑製ERK的激活,可部分逆轉因HSP90錶達增加而引起的腸癌細胞中VEGF錶達量的增加.結論 HSP90-ERK-VEGF通路在腸癌所緻血管生成中髮揮中重要作用.
목적 탐토열휴극단백90(HSP90)-세포외신호조절격매(ERK)-혈관내피생장인자(VEGF)신호통로재장암소치혈관내피세포천이화관상생성중작용급가능궤제.방법 개변장암세포HCT116중HSP90적표체수평,관찰대하유분자ERK린산화격활화VEGF표체적영향;장암세포조건배양상청자격인제정맥혈관내피(HUVECs)세포,관찰HUVECs세포재해배양액중천이화관상생성적능력;동시채용ERK억제제U0126화인중조VEGF단백,관찰가부부분역전인장암세포중HSP90표체개변대혈관세포활성적영향.결과 TNM분기Ⅱ、Ⅲ、Ⅳ적장암환자암조직중VEGF표체량고우대응암방조직.고표체HSP90증가료VEGF개도적HUVECs세포천이화혈관생성적능력.U0126처리장암세포후,억제ERK적격활,가부분역전인HSP90표체증가이인기적장암세포중VEGF표체량적증가.결론 HSP90-ERK-VEGF통로재장암소치혈관생성중발휘중중요작용.
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.