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Archive > Volume 31 Issue 5 > 2024,31(5):469-476. DOI:10.3872/j.issn.1007-385X.2024.05.006 Prev Next
Basic Research
Combined application of berberine and XAV939 inhibits the migration and apoptosis of osteosarcoma cells MG-63
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Abstract:
Objective: To investigate the effects of berberine (BBR) combined with XAV939 on the migration and apoptosis of osteosarcoma MG-63 cells and its possible mechanisms. Methods: MG-63 cells were cultured, and 20~120 μmol/L of BBR and 5~60 μmol/L of XAV939 were added, respectively. The cytotoxicity of BBR and XAV939 was determined by CCK-8 assay, and the MG-63 cells were randomly divided into the blank control (NC) group, the BBR group, the XAV939 group, and the BBR+XAV939 combined group. The effects of BBR and XAV939 treatment alone or in combination on the migratory ability of MG-63 cells were detected by the scratch healing assay and the Transwell assay. Hoechst 33258 staining, JC-1 staining and Annexin Ⅴ-FITC/PI double staining flow cytometry were used to detect the effects on cell mitochondrial membrane potential and apoptosis. Immunofluorescence was used to datect the expression of BAX protein, WB assay was used to detect the effects on the expression of MMP-2 and BAX in the cells, and qPCR was used to detect the effects on the expression of the MMP-2 gene. Results: BBR and XAV939 inhibited the proliferation of MG-63 cells in a dose-dependent manner, and 30 μmol/L BBR, 7.5 μmol/L XAV939 were selected for subsequent experiments. Compared with the NC group, 24 h after the cells were treated with BBR (30 μmol/L), XAV939 (7.5 μmol/L) and BBR+XAV939 combination, the migration ability of MG-63 cells was significantly reduced; apoptotic cells were significantly increased (all P<0.05); the mitochondrial membrane potential was decreased (P<0.01); the gene expression of MMP-2, and MMP-2, BAX protein levels were all reduced (all P<0.05). In addition, the effect of the combination group was significantly stronger than that of the monotherapy group (P<0.05 or P<0.01). Conclusion: BBR and XAV939 alone or in combination can inhibit the migration and promote the apoptosis of MG-63 cells. The mechanism may be related to the decreased expression of migration-related protein MMP-2 and increased level of apoptosis-related protein BAX.
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