FBXL20对胃癌细胞增殖、迁移及侵袭的影响

Effect of FBXL20 on Proliferation, Migration and Invasion of Gastric Cancer Cells

目的探讨FBXL20在胃癌细胞中的表达及其在胃癌细胞增殖、迁移和侵袭中的作用和机制。方法 Western blot检测人胃癌细胞系(BGC-823、AGS、MKN-45)及胃黏膜上皮细胞系(GES-1)中FBXL20蛋白的表达。靶向FXBL20 shRNA慢病毒载体抑制AGS细胞中FBXL20表达,CCK-8实验检测细胞增殖能力,Transwell实验检测细胞迁移和侵袭能力。Westernblot检测抑制FBXL20后Wnt通路中相关蛋白水平变化。结果与胃黏膜上皮细胞系相比,胃癌细胞系中FBXL20的表达明显增加(P<0.05)。与对照组相比,抑制FBXL20的AGS细胞在增殖、迁移和侵袭能力方面明显降低(P<0.05)。抑制FBXL20能降低GSK-3β的泛素化降解,导致Wnt通路中GSK-3β、p-GSK-3βTyr216的表达增加,而β-catenin、p-β-catenin、Cyclin D1及E-cadherin的表达降低。结论 FBXL20可能通过调控Wnt通路促进胃癌细胞的增殖、迁移和侵袭。

Objective To detect the expression of FBXL20 in gastric cancer cells, and determine its effect on the proliferation, migration and invasion of gastric cancer cells. Methods The expression levels of FBXL20 in gastric cancer cell lines BGC-823, AGS, MKN-45 and normal gastric epithelial cell line GES-1 were determined by Western blot. FBXL20 expression in AGS cells was inhibited by targeting FBXL20 shRNA lentiviral vectors. CCK-8 assay and Transwell assay were used to evaluate the proliferation, migration and invasion of AGS cells. The expression of Wnt pathway-related proteins were determined by Western blot. Results FBXL20 expression was significantly up-regulated in gastric cancer cell lines, compared with the normal gastric epithelial cell line (P<0.05). Compared with the control group, AGS cells with FBXL20 knockdown had lower proliferation, migration and invasion abilities (P<0.05). Inhibition of FBXL20 reduced ubiquitination degradation of GSK-3β, which increased the expression levels of GSK-3β, p-GSK-3βTyr216, and decreased the expression levels of β-catenin, p-β-catenin, Cyclin D1 and E-cadherin. Conclusion FBXL20 may promote the proliferation, migration and invasion of gastric cancer cells by regulating Wnt pathway.