目的：探讨GSK-3β在钙黏蛋白17（CDH17）介导的胃癌细胞侵袭中的作用及机制。方法：分别用CDH17 siRNA转染或GSK-3β抑制剂SB216763处理胃癌MKN-45细胞，以无处理和转染空载体的MKN-45细胞为空白对照及阴性对照，检测各组细胞GSK-3β、β-cantenin、NF-κB（p50/p65）的表达以及侵袭力变化。结果：与空白对照细胞比较，CDH17 siRNA转染后的MKN-45细胞CDH17、磷酸化GSK-3β、β-cantenin与p50/p65蛋白表达均明显降低，侵袭细胞数明显减少（均P<0.05）；SB216763处理后的MKN-45细胞CDH17与β-cantenin表达无明显变化（均P>0.05），磷酸化GSK-3β与p50/p65表达明显降低，侵袭细胞数明显减少（均P<0.05）；转染空载体的MKN-45细胞各项指标均无明显变化（均P>0.05）。结论：在CDH17介导的胃癌细胞侵袭信号通路中，GSK-3β可能处于β-cantenin下游，通过其磷酸化水平而调节NF-κB活性的关键分子。
Role of GSK-3β in cadherin 17-mediated gastric cancer cell invasion and the mechanism
Objective: To investigate the role of glycogen synthase kinase 3β (GSK-3β) in cadherin 17 (CDH17)-mediated of gastric cancer cell invasion and the mechanism. Methods: Gastric cancer MKN-45 cells were transfected with CDH17 siRNA or exposed to GSK-3β inhibitor SB216763 respectively, with untreated and empty vector transfected MKN-45 cells as blank control and negative control, respectively. The changes in GSK-3β, β-cantenin and NF-κB (p50/p65) expressions and invasion ability of each group of cells were determined. Results: Compared with blank control cells, in MKN-45 cells transfected with CDH17 siRNA, the CDH17, phosphorylated GSK-3β, β-cantenin and p50/p65 expressions were significantly decreased, and the number of invaded cells was significantly reduced (all P<0.05). In MKN-45 cells exposed to SB216763, the CDH17 and β-cantenin expressions showed no significant difference (both P>0.05), while the phosphorylated GSK-3β and p50/p65 expressions were significantly decreased, and number of invaded cells was significantly reduced (all P<0.05). In MKN-45 cells transfected with empty vectors, all parameters showed no significant change (all P>0.05). Conclusion: In the signaling pathway of CDH17-medated gastric cancer cell invasion, GSK-3β may be an important molecule downstream to β-cantenin for regulating NF-κB activity through its phosphorylation level.