Thymidine phosphorylase expressed in macrophages enhances antitumor effect of 5'-deoxy-5-fluorouridine on human colorectal carcinoma cells.
Anticancer Res
; 23(1A): 323-9, 2003.
Article
en En
| MEDLINE
| ID: mdl-12680231
ABSTRACT
BACKGROUND:
Thymidine phosphorylase (dThdPase) is a key enzyme in the activation of the pro-drugs of 5-fluorouracil (5-FU), 5-deoxy-5-fluorouridine (5'-DFUR) and capecitabine. In colorectal carcinoma (CRC), the major cells expressing dThdPase have been shown to be stromal cells, particularly macrophages. MATERIALS ANDMETHODS:
The present study was designed to clarify whether dThdPase expressed in macrophage-like cell lines, THP-1 and U937, and monocyte-rich mono-nuclear cells (MoMNCs) from human peripheral blood can modulate the antitumor effect of 5'-DFUR on CRC cells.RESULTS:
dThdPase protein was found in THP-1 and U937 by ELISA, while little or no dThdPase could be detected in the CRC cell lines tested. Incubation of 5'-DFUR with the macrophage-like cells significantly enhanced the antitumor effect of 5'-DFUR in a 5-DFUR sensitivity assay compared with untreated 5'-DFUR. MoMNCs also showed a similar effect. When the media containing 5'-DFUR was treated with either THP-1 or U937 cells, detectable levels of 5-FU could be measured in the treated media.CONCLUSION:
These data suggest that macrophages convert 5'-DFUR to 5-FU and release the converted 5-FU, resulting in an enhancement of the antitumor effect of 5'-DFUR.
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Colección:
01-internacional
Asunto principal:
Timidina Fosforilasa
/
Neoplasias Colorrectales
/
Floxuridina
/
Macrófagos
/
Antimetabolitos Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Anticancer Res
Año:
2003
Tipo del documento:
Article
País de afiliación:
Japón