糖原合成激酶-3β调控胰腺癌细胞迁移、侵袭和上皮间质转化的实验研究  

In-vitro study of glycogen synthase kinase-3β on regulation of migration, invasion and epithelial-mesenchymal transition in pancreatic cancer cells

作　　者：周伟[1] 章孟[1] 王晓川[1] 李永峰[1] 吴河水[1] 王春友[1] 刘涛[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院胰腺外科,武汉430022

出　　处：《中华普通外科杂志》2014年第11期853-856,共4页Chinese Journal of General Surgery

基　　金：国家自然科学基金资助（项目编号：81302115;81272658）

摘　　要：目的 在体外水平探讨糖原合成激酶-3β（glycogen synthase kinase 33,GSK-3β）在调控胰腺癌细胞迁移、侵袭和上皮间质转化中发挥的作用.方法 使用慢病毒干扰技术抑制胰腺癌细胞系中GSK-3β的表达,通过Western blot检测其对于GSK-3β磷酸化分子及上皮间质转化及侵袭转移能力相关分子表达的影响.通过划痕实验和Transwell实验检测抑制GSK-3β对胰腺癌细胞迁移和侵袭能力的影响.使用荧光素酶报告基因技术检测抑制GSK-3β对于核因子κB活性的影响. 结果 抑制胰腺癌细胞中GSK-3β的表达可以抑制胰腺癌细胞的迁移、侵袭能力以及上皮间质转化.抑制GSK-3β后ASPC-1和PANC-1组迁移抑制率分别为59.1％±6.4％和55.9％±7.3％,NF-κB的结合活性分别降至24.8％±3.1％和31.5％±5.4％,与对照组相比差异均有统计学意义（均P＜0.05）.结论 GSK-3β参与胰腺癌迁移、侵袭以及上皮间质转化的调控.抑制GSK-3β可以有效抑制胰腺癌迁移、侵袭以及上皮间质转化的发生,NF-κB是GSK-3β调控胰腺癌恶性生物学行为的关键分子.Objective To explore the role of GSK-3β in migration,invasion,metastasis and epithelial-mesenchymal transition of pancreatic cancer in vitro.Methods Lentiviral interference was used to inhibit the expression of GSK-3β in pancreatic cancer cells.Western blotting was used to detect expression of GSK-3β phosphorylation molecules and epithelial-mesenchymal transition and invasion related molecule.Scratch test and transwell test were adopted to detect the effect of GSK-3β inhibition on cell migration and invasion in pancreatic cancer cells.Luciferase reporter gene test was used to detect the effect of GSK-3β inhibition on NF-κB binding activity.Results Inhibition of GSK-3β expression significantly restrain migration,invasion and epithelial-mesenchymal transformation.Migration inhibitory rate was 59.1% ±6.4% in ASPC-1 group and 55.9% ± 7.3% in PANC-1 group.GSK-3β inhibition affected the activity of NF-κB,the binding activity decreased to 24.8% ± 3.1% and 31.5% ±5.4%,respectively （all P 〈 0.05）.Conclusions GSK-3β participates in the regulation of migration,invasion,and epithelialmesenchymal transition of pancreatic cancer.GSK-3β inhibition could surpress proliferation,invasion and epithelial-mesenchymal transformation,and NF-κB might be the key molecule in the regulation of pancreatic malignant behavior.

关 键 词：胰腺肿瘤 糖原合成酶激酶3 肿瘤侵润 迁移 上皮间质转化 

分 类 号：R735.9[医药卫生—肿瘤]