Dihydromyricetin (DHM) has diverse functions such as anti-inflammation, anti-oxidation, anti-alcohol intoxication, reducing blood pressure, anti-bacterial and anti-tumor properties. However, the effects of DHM on osteosarcoma and its underlying mechanisms are still not well understood. Herein, we investigated the anti-metastatic properties of DHM in human osteosarcoma U2OS and HOS cells. We found that DHM inhibits cell migration and invasion on osteosarcoma cell lines. In addition, DHM inhibits metastasis through down-regulating urokinase-type plasminogen activator (uPA) expression. Moreover, real-time polymerase chain reaction and promoter activity assays showed that DHM decreased uPA expression at the transcriptional level. Furthermore, inhibiton of uPA expression was associated with the suppression of promoter of Sp-1 and NF-κB on uPA. Regardless of blocking or activating of the extracellular signal-regulated kinase (ERK) pathway verified that DHM-suppressed uPA and cell invasion was through downregulating activation ERK pathway. In conclusion, our results suggest that DHM suppresses osteosarcoma invasion/migration via inhibiting ERK pathway mediated nuclear translocation of Sp-1 and NF-κB to further suppress uPA expression. DHM may be a potential therapeutic tool for metastasis of osteosarcoma.
