干扰素γ增加去氧氟尿苷和5-氟尿嘧啶抗膀胱癌作用的实验研究

Interferon gamma enhances the cytotoxicity of 5′-deoxy-5-fluorouridine and 5-fluorouracil against human bladder cancer cells

目的 探讨干扰素γ在膀胱癌T2 4细胞中对血小板衍化内皮细胞生长因子 /胸苷磷酸化酶 (PD ECGF/TP)表达的调节作用及其与去氧氟尿苷和 5 氟尿嘧啶抗癌作用的关系。 方法 分别用RT PCR和Western印迹检测PD ECGF/TPmRNA和蛋白质的表达 ,MTS法确定去氧氟尿苷和 5 氟尿嘧啶对膀胱癌T2 4细胞的细胞毒性作用。 结果 干扰素γ增强膀胱癌T2 4细胞表达PD ECGF/TP ,并使去氧氟尿苷的半数致死量 (IC50 )从 (16 .0± 3.6 )mmol/L降至 (6 .2± 0 .9)mmol/L(P<0 .0 1) ,5 氟尿嘧啶的IC50 从 (82 6 .7± 15 5 .1) μmol/L降至 (346 .7± 38.9) μmol/L(P <0 .0 5 )。 结论 干扰素γ通过诱导膀胱癌T2 4细胞表达PD ECGF/TP增强去氧氟尿苷和 5 氟尿嘧啶的抗癌作用 ,提示联合应用干扰素γ和去氧氟尿苷或 5 氟尿嘧啶可能提高膀胱癌的化疗效果。

Objective To investigate the regulative effect of interferon gamma (INFγ) on the expression of platelet-derived endothelial cell growth factor / thymidine phosphorylase (PD-ECGF/TP) and its relation with the anti-cancer effect of 5′-deoxy-5-fluorouridine (5'DFUR) and 5-fluorouracil (5FU) in T24 bladder cancer cells. Methods PD-ECGF/TP mRNA and protein expressions were determined by RT-PCR and Western blot,respectively.Cytotoxicity of 5′DFUR,5FU or mitomycin C (MMC) against T24 cells was evaluated by MTS assay. Results The expressions of PD-ECGF/TP mRNA and protein were concomitantly elevated in T24 cells after INFγ treatment.And INFγ decreased IC 50 s of 5′DFUR [from (16.0± 3.6 )mmol/L to (6.2±0.9)mmol/L,( P < 0.01)] and 5FU [from (826.7±155.1)μmol/L to (346.7±38.9) μmol/L,( P < 0.05)] in T24 cells.However,it did not alter IC 50 of MMC,which is not a substrate of PD-ECGF/TP. Conclusions INFγ enhances cytotoxicity of 5′DFUR and 5FU against human bladder cancer cells through induction of PD-ECGF/TP,which suggests INFγ/5′DFUR or INFγ/5FU combination treatment may result in better chemotherapeutic effecacy in human bladder cancers.