Anti-Invasive and Anti-Migratory Effects of Ononin on Human Osteosarcoma Cells by Limiting the MMP2/9 and EGFR-Erk1/2 Pathway

Abstract

Osteosarcoma is a common malignancy of the bone. Due to its high metastatic properties, osteosarcoma becomes the leading cause of cancer death worldwide. Ononin is an isoflavone glycoside known to have various pharmacological properties, including antioxidant and anti-inflammatory activities. In the present study, we aimed to investigate the efficacy of ononin on osteosarcoma cell migration, invasion, and the underlying mechanisms. The in vitro anti-tumorigenic and anti-migratory properties of ononin were determined by MTT, colony formation, invasion, and migration in MG-63 and U2OS osteosarcoma cell lines. The results were compared with the standard chemotherapeutic drug, doxorubicin (DOX), as a positive control. The dose-dependent manners of ononin treatment increased the expression of apoptosis and inhibition of cell proliferation through the EGFR-Erk1/2 signaling pathways. Additionally, ononin significantly inhibited the invasion and migration of human osteosarcoma cells. For consistency, we used the MG-63-xenograft mice model to confirm the in vivo anti-tumorigenic and anti-migratory efficacy of ononin by inhibiting the protein expressions of EGFR-Erk1/2 and MMP2/9. According to the histological study, ononin had no adverse effect on the liver and kidney. Overall, our findings suggested that ononin could be a potentially effective agent against the development and metastasis of osteosarcoma.