精神分裂症相关蛋白Dysbindin在胰腺癌中的作用

The function of Dysbindin,a protein related to schizophrenia,in pancreatic cancer

目的研究肌营养不良短小蛋白结合蛋白(Dysbindin)在胰腺癌中的作用及其与胆碱能激动剂卡巴胆碱的关系。方法通过慢病毒和小干扰RNA分别构建Dysbindin上调组和下调组胰腺癌细胞系,通过Transwell实验验证Dysbindin和卡巴胆碱对胰腺癌细胞侵袭转移的影响,通过蛋白质印迹实验验证卡巴胆碱对Dysbindin的影响以及卡巴胆碱和Dysbindin分别对上皮间质转化(EMT)相关分子的影响。结果Dysbindin上调组胰腺癌细胞转移侵袭能力增强,且与对照组相比,Dysbindin上调组上皮型钙黏蛋白减少[(0.94±0.00)比(0.74±0.08)],而神经型钙黏蛋白(N-cadherin)增加[(0.60±0.17)比(1.33±0.10)],且Snail增加[(0.43±0.11)比(0.81±0.06)],差异均具有统计学意义(P<0.05),而Dysbindin下调组结果相反。与对照组相比,卡巴胆碱实验组胞质紧密粘连蛋白1增加[(0.16±0.06)比(1.40±0.15)],且N-cadherin减少[(1.34±0.13)比(1.03±0.14)],差异均具有统计学意义(P<0.05)。结论Dysbindin能促进胰腺癌细胞的侵袭转移及EMT转化,卡巴胆碱能抑制Dysbindin的表达以及胰腺癌细胞的侵袭转移和EMT进程。

Objective To study the effect of dystrobrevin binding protein1(Dysbindin)in pancreatic cancer and the correlations between Dysbindin and the cholinergic agonist Carbachol.Methods Pancreatic cancer cell lines with Dysbindin overexpressed or knocked down were constructed by lentivirus based lentivirus or small interference RNA respectively,and the function of Dysbindin and Carbachol on invasion and metastasis of pancreatic cancer cells were investigated by Transwell migration and invasion assay,and the effects of Dysbindin and Carbachol on epithelial mesenchymal transition(EMT)related molecules were detected by Western Blot.Results When Dysbindin was overexpressed,pancreatic cancer migration and invasion were increasedand compared with control group,expression of E-cadherin was decreased[(0.94±0.00)vs(0.74±0.08)],but N-cadherin[(0.60±0.17)vs(1.33±0.10)]and Snail1 was increased[(0.43±0.11)vs(0.81±0.06)],the differences were statistically significant(P<0.05),and when Dysbindin was blocked,tumor migration and invasion were inhibited.Carbachol can inhibit the expression of Dysbindin,but increase ZO-1[(0.16±0.06)vs(1.40±0.15)]and N-cadherin level[(1.34±0.13)vs(1.03±0.14)],the differences were statistically significant(P<0.05).Conclusions Dysbindin can promote metastasis and EMT in pancreatic cancer.And Carbachol can decrease Dysbindin expression and inhibit metastasis and EMT of pancreatic cancer.