Down-regulation of Gankyrin Inhibits Gastric Cancer Cell Proliferation via Regulating β-Catenin/Cyclin D1 Signaling Pathway / 胃肠病学

ABSTRACT

Background:Gankyrin is an ankyrin repeat oncoprotein overexpressed and involved in the tumorigenesis and progression of various cancers. Aims:To investigate the effect and underlying mechanism of down-regulation of gankyrin expression on proliferation of gastric cancer cells. Methods:Lentivirus vector carrying gankyrin-targeted siRNA was transfected into human gastric cancer cell line MKN28. Cell proliferation,cell cycle distribution and β-catenin/ cyclin D1 signaling pathway was analyzed by MTT assay,flow cytometry and Western blotting,respectively,in gankyrin-silenced MKN28 cells and control cells. Results:The transfection efficiency of lentivirus vector was more than 90% ,and the protein expression of gankyrin in gankyrin siRNA transfected MKN28 cells was significantly repressed( P ﹤ 0. 01). Compared with cells transfected with control lentivirus and cells without transfection,MKN28 cells transfected with gankyrin siRNA showed markedly repressed cell growth after 3-day-culture;the proportion of cells in cell cycle G1 phase was significantly increased,and that in S phase was significantly decreased;down-regulated expression of β-catenin and cyclin D1 was observed(P all ﹤ 0. 01). Conclusions:Down-regulation of gankyrin expression in gastric cancer cells may induce cell cycle G1 phase arrest and inhibit cell proliferation by suppressing β-catenin/ cyclin D1 signaling pathway. Gankyrin might be a promising novel target for targeted therapy of gastric cancer.