Comparative antitumor activity of 5-fluorouracil and 5'-deoxy-5-fluorouridine in combination with interferon gamma in renal cell carcinoma cell lines.
The treatment of advanced renal cell carcinoma (RCC) remains unsatisfactory, and conventional therapy using interferon (IFN) has shown limited antitumor action. In this study, we examined the combined effects of IFN gamma with 5-fluorouracil (5-FU) as well as 5'-deoxy-5-fluorouridine (5'-DFUR), a prodrug of 5-FU, in vitro. The sensitivity of 4 RCC cell lines to IFN gamma and 5-FU or 5'-DFUR was evaluated using the MTT assay. The IC50 value for the cytostatics was expressed as the concentration at which growth was inhibited by 50% as compared with the control value. Thymidine phosphorylase (TP), the enzyme that converts 5'-DFUR into 5-FU and 5-FU into 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), was estimated by ELISA. As a result, a significant correlation between TP expression and sensitivity to 5-FU and 5'-DFUR was found in all 4 RCC cell lines. By adding 12.5 U/ml of IFN gamma, which is a concentration that does not affect cell proliferation, the TP expression significantly increased by 1.5 to 3.4 times in the 4 RCC cell lines. Susceptibility to 5-FU and 5'-DFUR was also significantly induced by 1.42 to 2.36 times and 2.9 to 5.71 times, respectively, in the 4 cell lines. These results suggested that TP may be useful as a predictive factor in combination therapy with IFN gamma and 5-FU or 5'-DFUF, which may be a promising treatment for advanced RCC.
Ikemoto
Shinichi
S
Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Sugimura
Kazunobu
K
Yoshida
Naomasa
N
Kuratsukuri
Katsuyuki
K
Wada
Seiji
S
Nakatani
Tatsuya
T
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D005467:Floxuridine / Q000008:administration & dosage / Q000494:pharmacology; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011355:Prodrugs / Q000008:administration & dosage; D011994:Recombinant Proteins; D013939:Thymidine Phosphorylase / Q000096:biosynthesis / Q000378:metabolism; D014407:Tumor Cells, Cultured
D011355:Prodrugs; D011994:Recombinant Proteins; D005467:Floxuridine; D007371:Interferon-gamma; D013939:Thymidine Phosphorylase; D005472:Fluorouracil; C025034:doxifluridine