Taurolidine 联合X射线对小鼠恶性黑色素瘤细胞周期进程的影响

目的：观察taurolidine联合X射线照射对小鼠恶性黑色素瘤（B16-4A5和B16-F10）细胞周期进程的影响，探讨其诱导肿瘤细胞凋亡的发生机制。方法：选择B16-4A5和B16-F10细胞系按给药浓度随机分为4组，taurolidine剂量分别为0、25、50和100  μmol.L^-1，同时进行1、2和4 Gy X射线照射，采用流式细胞术检测细胞凋亡率和细胞周期，Western blotting分析cyclin B、cdc2和caspase-3的表达。结果：与25  μmol.L^-1 taurolidine组比较， 50和100  μmol?L-1 taurolidine组诱导B16-4A5和B16-F10细胞发生_G0/_G1期阻滞，细胞数分别升高54.9%、73.7%和36.8%、55.5%（P＜0.05）； 50  μmol.L^-1 taurolidine联合2和4 Gy X射线照射组，细胞G2/M期阻滞消除，细胞数分别降低52.1%、44.2%和59.3%、52.7%（P＜0.05）。与对照组、单纯taurolidine组及单纯照射组比较，联合4 Gy X射线照射组cyclin B和cdc2的表达降低，caspase-3的表达升高（P＜0.05）。结论：taurolidine联合X射线照射可去除G2/M期阻滞，可选择地抑制肿瘤细胞cyclin B和cdc2的表达、增强caspase-3的表达，共同诱导细胞凋亡。

Effects of taurolidine in combination with X-rays irradiation on cell cycle progression of murine melanoma cells

Objective To evaluate the effects and mechanisms of taurolidine in combination with X-rays irradiation on cell cycle progress of murine melanoma cells,and provide a new idea of malignant tumor clinical treatment.Methods B16-4A and B16-F10 cells were divided into 4 groups according to the concentrations of taurolidine(0,25,50 and 100 μmol·L-1),respectively and combined with 1,2 and 4 Gy X-rays irradiation.The apoptotic rate and cell cycles were detected by flow cytometry.The expressions of cyclinB,cdc2,and caspase-3 were detected by Western blotting.Results Compared with 25 μmol·L-1 taurolidine group,the arrest of G2/M phase of B16-4A and B16-F10 cells after treated with 50 and 100 μmol·L-1 taurolidine was found and the cell numbers were increased by 54.9%,73.7% and 36.8%,55.5%,respectively(P<0.05).The arrest of G2/M phase of B16-4A and B16-F10 cells was also found and the cell numbers were decreased by 52.1%,44.2% and 59.3%,52.7%(P<0.05),respectively,after treated with 50 μmol·L-1 taurolidine in combination with 2 and 4 Gy X-rays irradiation.Therefore,the increase of caspase 3 expression and the decrease of cyclin B and cdc2 expressions were induced by the combination of 50 μmol·L-1 taurolidine with 2 and 4 Gy X-rays irradiation compared with control,taurolidine alone and irradiation alone groups.Conclusion Taurolidine in combination with X-rays irradiation can delete the G2/M arrest,supress the expressions of cyclin B and cdc2,increase the expression of caspase-3 and induce the apoptosis.