Combined effects of docetaxel and fluoropyrimidines on tumor growth and expression of interleukin-6 and thymidine phosphorylase in breast cancer xenografts

Citation
S. Yamamoto et al., Combined effects of docetaxel and fluoropyrimidines on tumor growth and expression of interleukin-6 and thymidine phosphorylase in breast cancer xenografts, CANC CHEMOT, 48(4), 2001, pp. 283-288
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER CHEMOTHERAPY AND PHARMACOLOGY
ISSN journal
0344-5704 → ACNP
Volume
48
Issue
4
Year of publication
2001
Pages
283 - 288
Database
ISI
SICI code
0344-5704(200110)48:4<283:CEODAF>2.0.ZU;2-5
Abstract
Purpose: Although several combination treatments with docetaxel and other a ntitumor agents have been tested in experimental and clinical studies, thei r synergistic effects are still ill-defined. The degree of synergism betwee n docetaxel and two oral fluoropyrimidines, tegafur and 5 ' -deoxy-5-fluoro uridine (5 ' -dFUrd), was investigated in the KPL-4 human breast cancer xen ograft model. Methods: Because this KPL-4 cell line secretes interleukin-6 (IL-6) and induces cachexia, the effects of the combined treatment on serum IL6 levels and cachectic markers were investigated. In addition, the expre ssion levels of thymidine phosphorylase (dThdPase), a key enzyme for conver ting 5 ' -dFUrd to 5-fluorouracil, were determined. Female nude mice bearin g KPL-4 tumors were treated orally with 5 ' -dFUrd (60 mg/kg, five times a week) or tegafur (100 mg/kg, five times a week) and by intraperitoneal inje ction of docetaxel (5 or 10 mg/kg, once a week). Results: Although docetaxe l (5 mg/kg) alone did not decrease either tumor growth or serum IL-6 levels , docetaxel (5 mg/kg) plus 5 ' -dFUrd or tegafur enhanced tumor growth inhi bition and decreased serum IL-6 levels more than 5'dFUrd or tegafur alone. Docetaxel (5 mg/kg) alone slightly increased the percentage of dThdPase-pos itive tumor cells., but the combined treatment with docetaxel plus 5 ' -dFU rd or tegafur significantly decreased the percentage of dThdPase-positive c ells in the KPL-4 tumors. Conclusion: These findings indicate that docetaxe l may stimulate dThdPase expression in tumor tissues and may enhance the an titumor activity of oral fluoropyrimidines. In addition, combined treatment with docetaxel and oral fluoropyrimidines may decrease serum IL-6 levels a nd may ameliorate IL-6-induced cancer cachexia.