胶质细胞源神经营养因子在胰腺癌神经侵袭中的作用及其机制  

Study of the effect and possible mechanism of glial cell line-derived neurotrophic factor in pancreatic cancer neural invasion

作　　者：郭仁德[1] 顾建华[1] 张志斌[1] 王毅[1] 谷川[1] 

机构地区：[1]天津市第一中心医院普外科,300192

出　　处：《中华实验外科杂志》2015年第1期9-11,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81172103）

摘　　要：目的 探讨胶质细胞源神经营养因子（GDNF）在胰腺癌神经侵袭中的作用及其机制.方法 建立能够模拟胰腺癌细胞沿神经轴突浸润动态过程的体外实验模型——背根神经节细胞（DRG）与Capan-2人胰腺癌细胞株共同培养,并采用显微镜观察、侵袭速率计算、Western blot等方法,探讨胰腺癌细胞神经侵袭的动态过程、GDNF的作用机制以及阻断治疗的效果.结果 胰腺癌细胞、DRG共同培养可促进背根神经节神经突的生长;背根神经节对于胰腺癌细胞具有化学趋化作用,这种作用能够被GDNF抗体和丝裂原活化蛋白激酶通道（MAPK）阻断剂PD98059部分阻断;GDNF 40 μg/L组磷酸化细胞外信号调节激酶（p-ERK）的表达为0.09±0.01、1.85±0.11、1.92±0.06、1.87±0.15,其他3组与0min组比较差异均有统计学意义（P＜0.05）,细胞外信号调节激酶（ERK）的表达分别为1.53±0.04、1.53±0.11、1.51±0.09、1.49±0.12,各组之间差异无统计学意义（P＞0.05）;100 μg/L组p-ERK的表达为0.11±0.13、1.97±0.15、1.89±0.04、1.82±0.13,其他3组与0 min组比较差异均有统计学意义（P＜0.05）,ERK的表达分别为1.76±0.14、1.76 ±0.16、1.87±0.06、1.79±0.11,各组之间差异无统计学意义（P＞0.05）.GDNF可上调ERK磷酸化产物p-ERK的表达水平（P＜0.05）,而对于ERK的表达则无明显影响（P＞0.05）.结论 GDNF具有促胰腺癌细胞增殖分化和化学趋化作用,其作用介导过程有细胞外信号控制激酶Ras-Raf-分裂原活化抑制剂（MEK）-ERK途径的参与.Objective To investigate the effect and possible mechanism of glial cell line-derived neurotrophic factor （GDNF） in pancreatic cancer neural invasion.Methods Build a co-culture model of human pancreatic cancer cell line Capan-2 and rat dorsal root ganglias （DRG） to provide a new quantifiable in vitro model for the study of pancreatic cancer neural invasion.Make use of microscopy,invasion velocity counting,Western blotting to study the dynamic process of neural invasion of pancreatic cancer cells,the role of GDNF,the possible mechanism and the effect of blocker therapy.Results The co-culture of pancreatic cancer cell with DRG can accelerate the growth of neural axon,the DRG has chemotaxis effect for pancreatic cancer cells and the effect can be partly blocked by mitogen-activated protein kinases blocker PD98059 and anti-GDNF antibody,the expression of phosphorylated extracellular signal-regulated kinase （p-ERK） in GDNF 40 μg/L group is 0.09 ± 0.01,1.85 ± 0.11,1.92 ± 0.06,1.87 ± 0.15,the 0 min group is significantly higher than that in the other 3 groups （P 〈 0.05）.The expression of extracellular signal-regulated kinase （ERK） is 1.53 ±0.04,1.53 ±0.11,1.51 ±0.09,1.49 ±0.12 respectively and have no significant difference （P 〉 0.05）.The expression of p-ERK in 100 μg/L group is 0.11 ±0.13,1.97 ±0.15,1.89 ±0.04,1.82 ±0.13,the other 3 groups is significantly higher than that in the 0min group （P 〈 0.05）.The expression of ERK is 1.76 ± 0.14,1.76 ± 0.16,1.87 ± 0.06,1.79 ± 0.11 respectively and have no significant difference （P 〉 0.05）.GDNF can up-regulate the level of phosphorylation of ERK （P 〈 0.05） but has no significant effect on ERK （P 〉 0.05）.Conclusion GDNF has the chemotaxis effect and can stimulate the proliferation of pancreatic cancer cell,the Ras-Raf-mitogen activated protein kinase inhibtitor （MEK）-ERK pathway is involved in the process.

关 键 词：胶质细胞源神经营养因子 胰腺癌 神经侵袭 机制 

分 类 号：R735.9[医药卫生—肿瘤]