第10号染色体缺失的磷酸酶和张力蛋白的同源基因通过减少上皮-间充质转化来抑制胆管癌细胞QBC939的迁移能力

Phosphatase and tensin homolog deleted on chromosome 10 inhibits cholangiocarcinoma cell QBC939 migration through decreasing epithelial-mesenchymal transition

目的 探讨第10号染色体缺失的磷酸酶和张力蛋白的同源基因（PTEN）对胆管癌细胞株QBC939迁移能力的抑制作用及其机制.方法 取4μg PTEN质粒转染胆管癌细胞株QBC939,转染72 h后,采用Transwell迁移实验和Western blot检测上调PTEN对QBC939细胞迁移能力和上皮-间充质转化（EMT）中重要的分子标志物表达的影响.结果 人胆管癌细胞株QBC939经PTEN质粒转染72 h后,其通过基质膜细胞数目比较对照组数目减半（P＜0.01）,迁移能力减弱,与EMT相关分子标志物Slug、Snail、波形蛋白（Vimentin）蛋白表达水平降低,磷酸肌醇3激酶（PI3K）/蛋白激酶B（Akt）信号通路中的磷酸化Akt （p-Akt）蛋白表达也明显减少.结论 PTEN可以通过抑制EMT进而影响胆管癌细胞迁移,PTEN对EMT的抑制作用可能是由PI3K/Akt信号通路调节的.

Objective To investigate the effects of phosphatase and tensin homolog deleted on chromosome 10 （PTEN） on cholangiocarcinoma cell QBC939 migration and the mechanisms by which PTEN regulates QBC939 cell migration.Methods QBC939 cells were transfected with 4 μg PTEN-expression vector for 72 h.Transwell assay was used to detect the effects of PTEN on cholangiocarcinoma cell migration.Western blotting was used to determine the protein levels involving in epithelial-mesenchymal transition （EMT） and phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt） signaling pathway after PTEN was overexpressed in QBC939 cells.Results Overexpression of PTEN inhibited cholangiocarcinoma cell QBC939 migration as demonstrated by decreasing the ability of cells to migrate through the membrance in the Transwell migration assay （P 〈 0.01）.The enforced expression of PTEN inhibited EMT of QBC939 cells as demonstrated by decreasing Slug, Snail and Vimentin protein expression.In addition, upregulation of PTEN inhibited phosphorylation of Akt.Conclusion These results suggest PTEN inhibited cell migration through regulating EMT process in QBC939 cells;PTEN inhibited EMT process of QBC939 cells by inactivating the PI3K/Akt signal pathway.