Berberine inhibits the growth of osteosarcoma through modulating MMP/NM-23 and MAPK/JNK signal pathways.

OBJECTIVE

To investigate the effects and mechanisms of berberine (BBR) on the migration, invasion, proliferation and apoptosis of osteosarcoma cells in vitro.

METHODS

Proliferation of MG-63 and U2OS cells was measured by the CCK-8 assay. Cells migration was examined by wound-healing assay. The invasion and metastasis of cells were evaluated by transwell invasion assay. Cells apoptosis was determined by the flow cytometry. Caspase-3 activity in MG-63 and U2OS cells was measured, and Western blot was used to measure the levels of Bax, Bcl-2, MMP-2 and MMP-9 in cells. In addition, the osteosarcoma graft tumor model of mice was established. The tumorigenesis of MG-63 cells in nude mice was compared among three groups. Immunohistochemistry assay was used to measure the levels of MMP-2, MMP-9 and NM-23 in tumor tissue.

RESULTS

It was showed that BBR inhibited the proliferation of MG-63 and U2OS cells in vitro in time- and concentration-dependent manners. Moreover, BBR reduced the cells migration and invasion, also down-regulated the expressions of MMP-2 and MMP-9. BBR also inhibited the cells apoptosis by down-regulating the expression of Bcl-2 and up-regulating the expression of Bax. In nude mice, BBR obviously inhibited the tumorigenesis of MG-63 cells. Compared with the negative group, BBR decreased the levels of MMP-2 and MMP-9 and increased the level of NM-23. The molecular mechanism was associated with activation of the MAPK/JNK signal transduction pathway.

CONCLUSIONS

BBR significantly regulates the biological behaviors of osteosarcoma cells and inhibits the growth of osteosarcoma. The molecular mechanism may be associated with the modulation of MMP/NM-23 and MAPK/JNK signals. BBR may be a potential drug for the treatment of osteosarcoma.