丝裂霉素C与C_2-神经酰胺或抗Fas单克隆抗体联合治疗膀胱癌的体外研究

Effect of mitomycin C combined with C_2-ceramide or anti-Fas monoclonal antibody in human bladder cancer cells

目的:探讨丝裂霉素C(MMC)与C2-神经酰胺(C2-Cer)或抗Fas单克隆抗体(anti-FasmAb)联合应用对人膀胱癌BIU-87和T24细胞生长的抑制作用。方法:采用四甲基偶氮唑蓝(MTT)比色法测定MMC、C2-Cer、anti-FasmAb单独应用及MMC分别与C2-Cer或anti-FasmAb联合应用对人膀胱癌BIU-87和T24细胞生长的抑制作用,并应用CHOU-TALALAY联合指数法对药物联合应用的效果进行判定。结果:药物单用及MMC分别与C2-Cer、anti-FasmAb合用对BIU-87和T24细胞的生长均有抑制作用,药物合用时的中效浓度与单用时比较有不同程度的降低。MMC与C2-Cer合用时,对于BIU-87细胞,表现为协同作用(CI<1);对于T24细胞,低浓度(0%<fa<34%)时为协同作用(CI<1),高浓度(34%<fa<100%)时为拮抗作用(CI>1)。MMC与anti-FasmAb合用时,对于BIU-87细胞,在大部分效应范围(18%<fa<100%)为拮抗作用(CI>1);对于T24细胞,则在大部分效应范围(0<fa<74%)为协同作用(CI<1)。结论:药物联合应用的效果在不同膀胱癌细胞株之间存在差异,合理的联合用药可以降低药物浓度。

Objective：To study the anti-cancer effect of mitomycin C （MMC） combined with C2-ceramide （C2-Cer） or anti-Fas monoclonal antibody （anti-Fas mAb） in human bladder cancer cell lines BIU-87 and T24. Methods：The inhibitory effects of MMC,C2-Cer,anti-Fas mAb, and MMC combined with C2-Cer or anti-Fas mAb on BIU-87 and T24 cells were determined by MrlT assay, and the effect of the combination therapy was evaluated by combination-index method of CHOU and TALALAY. Results： The inhibitory effect was found when these 3 drugs were used alone or together. The median effect concentrations of these 3 drugs decreased to various extents when the drugs were used together. MMC was synergistic with C2-Cer in BIU-87 cells. In T24 cells, low concentration of MMC was synergistic with low concentration of C2-Cer,and high concentration of MMC was antagonistic to high concentration of C2-Cer. In the majority of effect range,MMC was antagonistic to anti-Fas mAb in BIU-87 cells and synergistic with anti-Fas mAb in T24 cells. Condusion： The effects of combination therapy are different in different bladder cancer cell lines. The concentrations of anticancer drugs may decrease in the combination therapy.