Enhancement of the anti-tumor activity of S-1 by low-dose cisplatin in mice bearing the sarcoma-180 model
Autor: | Toshiki Kamano, Kazuhiro Sakamoto, Akira Miyakawa, Shuichi Sakamoto, Seiya Hosoda, Satoshi Yurimoto, Atsushi Okuzawa |
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Rok vydání: | 2005 |
Předmět: |
Male
Cancer Research Pyridines Mice Inbred Strains Uridine Triphosphate Pharmacology Thymidine Kinase Thymidylate synthase Group A Tegafur Group B Mice Antineoplastic Combined Chemotherapy Protocols Mole medicine Animals Pharmacology (medical) RNA Neoplasm Sarcoma 180 Cisplatin biology Chemistry Body Weight Combination chemotherapy Drug Combinations Oxonic Acid Oncology Biochemistry Fluorouracil biology.protein medicine.drug |
Zdroj: | Anti-Cancer Drugs. 16:1109-1114 |
ISSN: | 0959-4973 |
DOI: | 10.1097/00001813-200511000-00010 |
Popis: | The combination of S-1, consisting of 1 mol/l tegafur, 0.4 mol/l 5-chloro-2,4-dihydroxypyridine and 1 mol/l potassium oxonate, plus low-dose cisplatin has showed promising anti-tumor activities in experimental and clinical studies. The aim of this study was to investigate the mechanism of this combination chemotherapy. Mice bearing sarcoma-180 cells were divided into groups of seven animals each - Group A: no treatment; Group B: 5-fluorouracil (5-FU) 10 mg/kg continuous i.p. infusion; Group C: S-1 10 mg/kg p.o.; Group D: cisplatin 0.2 mg/kg i.p.; Group E: B+D; Group F: C+D. Treatments were given for 5 consecutive days, and then anti-tumor activity, the concentration of 5-FU, the thymidylate synthase inhibition rate (TSIR) and the level of 5-FU incorporated into RNA (F-RNA) in tumor tissue were evaluated. Anti-tumor activity in Group F was higher than in any other group. A significantly higher concentration of 5-FU in tumor was detected in the S-1-treated groups (C and F) than in the 5-FU-treated groups (B and E). No differences in TSIR were observed between the groups treated with 5-FU or S-1 with or without cisplatin; however, the F-RNA level in Group F was about 1.24 times significantly higher than that in Group C. Group F showed the highest anti-tumor activity, with increasing intratumoral levels of 5-FU and F-RNA, but not that of TSIR. These results suggested that the superior anti-tumor activity obtained by S-1+cisplatin might be associated with an incorporation of 5-FU into RNA. |
Databáze: | OpenAIRE |
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