Inhibitory effects of wnt inhibitor IWR-1 on proliferation and migration of osteosarcoma MG-63 cells / 肿瘤

ABSTRACT

Objective: To investigate the effects of Wnt inhibitor IWR-1-endo (IWR-1) on the proliferation and migration of human osteosarcoma MG-63 cells, and to explore the possible mechanism. Methods: MG-63 cells were treated with different concentrations of IWR-1 (2, 4, 8 and 16 μmol/L). Then the growth inhibitory rates of MG-63 cells was determined by CCK-8 assay. The cell cycle and apoptosis rate of MG-63 cells were detected by FCM method. The migration ability of MG-63 cells was abserved by scratch wound healing assay. The expression levels of β-catenin and cyclin D1 mRNAs were detected by real-time fluorescent quantitative PCR. The expression levels of Axis inhibition protein 1 (AXIN1), β-catenin, phospho-β-catenin (p-β-catenin) and cyclin D1 proteins were detected by Western blotting. Results: The proliferation inhibitory rate of MG-63 cells after IWR-1 treatment increased in a time-and concentration-dependent manner (all P < 0.01). The proportion of MG-63 cells treated with IWR-1 in G0/G1 phase were increased (P < 0.05), and the apoptosis rate of MG-63 cells increased significantly with the increase of IWR-1 concentration (P < 0.01). IWR-1 reduced significantly the scratch healing rate of MG-63 cells (P < 0.01), decreased the mRNA (both P < 0.01) and protein (both P < 0.05) expression levels of β-catenin and cyclin D1, and increased the expression levels of AXIN 1 and p-β-catenin proteins (both P < 0.05). Conclusion: IWR-1 can inhibit the proliferation and migration of MG-63 cells by blocking Wnt/β-catenin signaling pathway.