γ干扰素诱导的PD-ECGF/TP上调增强了5-氟尿嘧啶和5'-脱氧-5-氟尿苷对膀胱癌细胞的细胞毒性。

IFN gamma-induced up-regulation of PD-ECGF/TP enhances the cytotoxicity of 5-fluorouracil and 5'-deoxy-5-fluorouridine in bladder cancer cells.

作者信息

Li Gang, Kawakami Satoru, Kageyama Yukio, Yan Chunyin, Saito Kazutaka, Kihara Kazunori

机构信息

Department of Urology and Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.

出版信息

Anticancer Res. 2002 Sep-Oct;22(5):2607-12.

PMID:12529971

Abstract

BACKGROUND

PD-ECGF/TP is an essential enzyme in converting 5'DFUR and 5FU to their active metabolites and can be up-regulated by some cytokines.

MATERIALS AND METHODS

PD-ECGF/TP mRNA and protein expressions were determined by RT-PCR and Western blot, respectively. The cytotoxicity of 5FU, 5'DFUR or MMC against RT-4 and T24 cells was evaluated by MTS assay. The PD-ECGF/TP expressions in primary bladder cancers were also analyzed.

RESULTS

Levels of PD-ECGF/TP mRNA and protein were concomitantly elevated in RT-4 and T24 cells after IFN gamma treatment. IFN gamma decreased the IC50 of 5FU and 5'DFUR in both cell lines, while it did not alter the IC50 of MMC, which is not a substrate of PD-ECGF/TP. PD-ECGF/TP expression correlated with tumor stage and grade in primary bladder cancers.

CONCLUSION

IFN gamma enhances the cytotoxicity of 5FU and 5'DFUR against human bladder cancer cells through induction of PD-ECGF/TP. The results imply that an IFN gamma/5FU or IFN gamma/5'DFUR combination therapy may be applicable to clinical bladder cancers.

摘要

背景

PD - ECGF/TP是将5'DFUR和5FU转化为其活性代谢产物的关键酶，且可被某些细胞因子上调。

材料与方法

分别通过逆转录聚合酶链反应（RT - PCR）和蛋白质免疫印迹法（Western blot）测定PD - ECGF/TP mRNA和蛋白表达。采用MTS法评估5FU、5'DFUR或丝裂霉素（MMC）对RT - 4和T24细胞的细胞毒性。还分析了原发性膀胱癌中PD - ECGF/TP的表达情况。

结果

干扰素γ（IFNγ）处理后，RT - 4和T24细胞中PD - ECGF/TP mRNA和蛋白水平同时升高。IFNγ降低了两种细胞系中5FU和5'DFUR的半数抑制浓度（IC50），而未改变MMC的IC50，MMC不是PD - ECGF/TP的底物。原发性膀胱癌中PD - ECGF/TP表达与肿瘤分期和分级相关。