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_临床医学论文.docVIP

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_临床医学论文 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_临床医学论文 作者：龚海洋，蔡郑东，郑龙坡，李国东，华莹奇 【摘要】 ［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、10 μmol/L时，MG63细胞凋亡率分别为9.91%、48.95%，单用甲氨蝶呤（1、10、100 mg／L）时细胞凋亡率为37.68%、45.93%、52.418%，当唑来膦酸(10 μmol/L)联合甲氨蝶呤（1、10、100 mg／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(0.01)。唑来膦酸作用MG63细胞72 h的IC50值为9.39 μmol/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。 【关键词】 骨肉瘤； MG63细胞系； 唑来膦酸； 甲氨蝶呤； 协同作用 Abstract: ［Objective］To explore the possible interest of therapeutic approaches including nitrogen-containing biphosphonate 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.IC50 value of zoledronic acid for therapy of MG63 after 72h was 9.39 μmol/L.The cell growth inhibition rates of MG63 at 72 h was 48.95% in zoledronic acid (10 μmol/L) group，and 37.68%,45.93% and 52.42% in methotrexate groups MTX（1,10 and 100 mg／L）.When combined treatment of zoledronic 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(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.