Inhibitory effect of lycorine on osteosarcoma and its underlying mechanism / 肿瘤

ABSTRACT

Objective: To investigate the inhibitory effect of lycorine on human osteosarcoma 143B cells and its underlying molecular mechanism. Methods: Osteosarcoma 143B cells were treated with 0-8 μmol/L lycorine, respectively. Then the effect of lycorine on the proliferation of 143B cells was detected by crystal violet staining, MTT and colony-forming assay. The migration and invasion abilities of 143B cells were detected by scratch wound healing assay and Transwell assay, respectively. The apoptosis of 143B cells was measured by hoechst 33258 staining. The expression levels of migration-and invasion-related proteins matrix metalloproteinase-7 (MMP-7) and MMP-9, as well as apoptosis-related proteins Bcl-2, Caspase 3 and cleaved Caspase 3 (c-Caspase 3) were detected by Western blotting. Furthermore, the transcription activity of T cell factor/ lymphoid enhancer factor (TCF/LEF) was detected by luciferase reporter gene system. The expression levels of β-catenin and its downstream target molecules Cyclin D1 and c-Myc in Wnt/β-catenin signaling pathway were detected by Western blotting. Results: Lycorine significantly inhibited the proliferation, migration and invasion abilities of osteosarcoma 143B cells, and promoted apoptosis (all P < 0.01). The expression levels of migration-and invasion-related proteins MMP-7 and MMP-9 in 143B cells treated with lycorine were down-regulated remarkably (all P < 0.05), and the expression of apoptosis-related protein Bcl-2 was down-regulated, while the expressions of Caspase 3 and c-Caspase 3 were up-regulated (all P < 0.05). The transcription activity of TCF/LEF was significantly decreased (P < 0.01), and the expression levels of β-catenin, c-Myc and Cyclin D1 were all decreased (all P < 0.05) after lycorine treatment. Conclusion: Lycorine may inhibit the proliferation, migration and invasion of human osteosarcoma 143B cells, and promote apoptosis by blocking the activity of Wnt/β-catenin signaling pathway.