In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 64, No. 5 ( 2004-03-01), p. 1794-1801
Abstract:
Thymidine phosphorylase (TP) catalyzes the reversible conversion of thymidine to thymine, thereby generating 2-deoxy-d-ribose-1-phosphate, which upon dephosphorylation forms 2-deoxy-d-ribose (d-dRib), a degradation product of thymidine. We have previously shown that d-dRib promotes angiogenesis and chemotaxis of endothelial cells and also confers resistance to hypoxia-induced apoptosis in some cancer cell lines. 2-Deoxy-l-ribose (l-dRib), a stereoisomer of d-dRib, can inhibit d-dRib anti-apoptotic effects and suppressed the growth of KB cells overexpressing TP (KB/TP cells) transplanted into nude mice. In this study, we examined the ability of l-dRib to suppress metastasis of KB/TP cells using two different models of metastasis. The antimetastatic effect of l-dRib was first investigated in a liver-metastasis model in nude mice inoculated with KB/TP cells. Oral administration of l-dRib for 28 days at a dose of 20 mg/kg/day significantly reduced the number of metastatic nodules in the liver and suppressed angiogenesis and enhanced apoptosis in KB/TP metastatic nodules. Next, we compared the ability of l-dRib and tegafur alone or in combination to decrease the number of metastatic nodules in organs in the abdominal cavity in nude mice receiving s.c. of KB/TP cells into their backs. l-dRib (20 mg/kg/day) was significantly (P & lt; 0.05) more efficient than tegafur (100 mg/kg/day) in decreasing the number of metastatic nodules in organs in the abdominal cavity. By in vitro invasion assay, l-dRib also reduced the number of invading KB/TP cells. l-dRib anti-invasive activity may be mediated by its ability to suppress the enhancing effect of TP and d-dRib on both mRNA and protein expression of vascular endothelial growth factor and interleukin-8 in cultured KB cells. These findings suggest that l-dRib may be useful in a clinical setting for the suppression of metastasis of tumor cells expressing TP.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-03-2597
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2004
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
Permalink
