[Enhancement effect of interferon gamma on the sensitivity of RT4 bladder cancer cells to 5'-deoxy-5-fluorouridine,and 5-fluorouracil through up-regulation of PD-ECGF/TP].
OBJECTIVE
Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is an essential enzyme in converting 5'-deoxy-5-fluorouridine (5'-DFUR), and 5-fluorouracil (5-FU) to their active metabolites in vivo, and can be up-regulated by some cytokines such as interleukin-1, and interferon gamma (INFgamma). This study was to observe the regulative effect of INFgamma on expression of PD-ECGF/TP, and its relation with the anti-cancer effect of 5'-DFUR, and 5-FU on RT4 bladder cancer cells.


METHODS
PD-ECGF/TP mRNA, and protein expression were determined by reverse transcriptase polymerase chain reaction (RT-PCR), and Western blot analysis, respectively. Cytotoxicity of 5'-DFUR, and 5-FU against RT4 cells was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymetho-xyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay.


RESULTS
Expression levels of PD-ECGF/TP mRNA and protein were elevated in RT4 cells after cultured with INFgamma. INFgamma reduced IC50s of 5'-DFUR [from (9.7+/-0.2) mmol/L to (3.7+/-0.9) mmol/L], and 5-FU [from (130.0+/-21.2) mmol/L to (49.3+/-18.4) mmol/L] in RT4 cells.


CONCLUSIONS
INFgamma enhances cytotoxicity of 5'-DFUR, and 5-FU against RT4 cells through induction of PD-ECGF/TP. INFgamma/5'-DFUR or INFgamma/5-FU combination treatment may lead to better chemotherapeutic results in human bladder cancer.
Li
Gang
G
Department of Urology, The First Affiliated Hospital, Suzhou University, Suzhou, Jiangsu, 215006, PR China. ligang8882000@yahoo.com.cn
Yan
Chun-Yin
CY
Wen
Duan-Gai
DG
Ding
Qiang
Q
Zhang
Yuan-Fang
YF
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005467:Floxuridine / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013939:Thymidine Phosphorylase / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D005467:Floxuridine; D007371:Interferon-gamma; D013939:Thymidine Phosphorylase; D005472:Fluorouracil; C025034:doxifluridine