Growth Inhibition And Sensitization To Methotrexate By Zoledronic Acid In Osteosarcoma Cells

ObjectiveSince osteosarcoma is a drug-resistant disease,the aim of the present study was to explore the possible interest of therapeutic approaches including nitrogen-containing biphosphonate zoledronic acid using osteosarcoma cell lines MG63,and to investigate whether there was a synergistic interaction between zoledronic acid and Methotrexate.MethodZoledronic acid alone or combined with anticancer drug Methotrexate were used to treat human ostoesarcoma cells line MG63.The cell growth inhibition were assessed by MTT.ResultsThere was a dose-dependent and time-dependent(1～100μmol/L)inhibition of cell proliferation by zoledronic acid.IC50 value ofzoledronic acid for therapy of MG63 after 72h was 9.39μmol/L.The cell growth inhibition rate of MG63 after 72h was 48.95%in zoledronic acid(10μmol/L)group,and 37.68%,45.93%,52.418%in Methotrexate groups MTX(1,10,100mg/L).When combined treatment ofzoledronic acid(10μmol/L)and Methotrexate(1,10,100mg/L) was used,the cell growth inhibition rates were 51.96%,66.77%,69.23%respectively,of MG63 cells in a time-and dose-dependent manner.Its IC50 value is 9.39μmol/L.Zoledronic acid has a synergistic effect with Methotrexate.These differences were significant(P<0.05).Zoledronic acid induces osteosarcoma cell death and cell cycle arrest in S phases.ConclusionsZoledronic acid has an explicit effect of inhibiting proliferation and induces osteosarcoma cell death and cell cycle arrest in S phases.