唑来膦酸联合甲氨蝶呤对骨肉瘤细胞生长及化疗敏感性研究

Growth inhibition and sensitization to methotrexate plus zoledronic acid in osteosarcoma cells

[目的]本试验主要观察第3代二膦酸盐类药物唑来膦酸(zoledronic acid,ZOL)在体外对人骨肉瘤细胞株MG63生长的影响,进一步研究唑来膦酸与甲氨蝶呤(methotrexate,MTX)合用对MG63细胞的生长抑制是否具有协同作用。[方法]采用MTT法分别检测不同剂量的唑来膦酸、甲氨蝶呤对人骨肉瘤细胞株MG63生长作用,检测唑来膦酸联合甲氨蝶呤对人骨肉瘤细胞株MG63的增殖抑制。[结果]唑来膦酸对MG63细胞的抑制效应与药物剂量及作用时间均成正比。单药唑来膦酸组剂量为1、10μmol/L时,MG63细胞凋亡率分别为9.91%、48.95%,单用甲氨蝶呤(1、10、100mg/L)时细胞凋亡率为37.68%、45.93%、52.418%,当唑来膦酸(10μmol/L)联合甲氨蝶呤(1、10、100mg/L)时MG63细胞的凋亡率分别为51.96%、66.77%、69.23%,联合用药组与单药组相比差异有显著性(P<0.01)。唑来膦酸作用MG63细胞72h的IC50值为9.39μmol/L。[结论]唑来膦酸对人骨肉瘤细胞株MG63有生长抑制作用,呈时间、剂量依赖性效应,唑来膦酸与甲氨蝶呤有协同作用。

[Objective] To explore the possible interest of therapeutic approaches including nitrogen -containing biphos-phonate zoledronic acid using osteosarcoma cell lines MG63, and to investigate whether there is a synergism between zoledronic acid and methotrexate.[Method] Zoledronic acid alone or combined with methotrexate was used to treat human ostoesarcoma cells line MG63. The cell growth inhibition was assessed by MTT.[ Result] There was a dose - dependent and time - dependent （1 - 100μmol/L） inhibition of cell proliferation by zoledronic acid. ICS0 value of zoledronic acid for therapy of MG63 after 72h was 9.39μmol/L. The cell growth inhibition rates of MG63 at 72 h was 48.95% in zoledronic acid （10μmol/L） group, and 37. 68%, 45.93% and 52.42% in methotrexate groups MTX （1,10 and 100mg/L） . When combined treatment of zole- dronic acid （10μmol/L） and methotrexate （1,10 and 100 mg/L） was used, the cell growth inhibition rates were 51.96%, 66.77% and 69. 23% , respectively. The combination of zoledronic acid and methotrexate demonstrated a synergistic effect. The differences were significant （P 〈 0.01 ）.[Conclusion] Zoledronic acid has an explicit effect of inhibiting proliferation of MG - 63 cells in a time-and dose - dependent manner. Its IC50 value is 9.39 μmol/L. Zoledronic acid could induce apoptosis and has a synergistic interaction with methotrexate.