Inhibitory effects of XAV939 on gastric carcinoma MKN-45 cells proliferation and Wnt/β-catenin signaling pathway in vitro

Abstract

Objective To investigate the effects of XAV939 on proliferation and and Wnt/β-catenin signaling pathway of MKN-45 cells in vitro.Methods MKN-45 cells were cultured with different concentrations of XAV939.The inhibition of cell proliferation was detected by methyl thiazol tetrazolium (MTT).The expression levels of β-catenin and cell cycle protein 1 (Cyclin D1) mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR),and the protein expression of Axin 1,β-catenin,p-β-catenin and Cyclin D1 by Western blotting.Results Inhibitory rate of MKN-45 cells treated with XAV939 for 48 h was 22.5％,39.1％,52.5％,and 62.1％ respectively (P ＜0.05).Different concentrations of XAV939 could down-regulate β-catenin and Cyclin D1 mRNA level (0.727 ±0.031,0.467 ±0.051,0.353 ±0.035,0.293 ±0.031,P＜0.05; 0.690±0.161,0.487 ±0.231,0.360 ±0.257,0.2 1 6 ± 0.197,P ＜ 0.05),down-regulate β-catenin and Cyclin D1 protein levels,but significantly up-regulate Axin 1 and p-β-catenin expression levels.Conclusion XAV939 can inhibite proliferation of MKN-45 cells,which may be associated with down-regulation of Wnt/β-catenin signaling pathway. Key words: Gastric carcinoma; Wnt/β-catenin signaling pathway; Cyclin D1