Potassium oxonate, an enzyme inhibitor compounded in S-1, reduces the suppression of antitumor immunity induced by 5-fluorouracil

• Published in: Cancer chemotherapy and pharmacology 2006-08, Vol.58 (2), p.183-188
• Main Authors: YAMASHITA, Tetsuro, UEDA, Yuji, FUJI, Nobuaki, ITOH, Tsuyoshi, KURIOKA, Hideaki, SHIRASAKA, Tetsuhiko, YAMAGISHI, Hisakazu
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Drug Combinations; Enzyme Inhibitors - pharmacology; Fluorouracil - antagonists & inhibitors; Gastroenterology. Liver. Pancreas. Abdomen; Immunophenotyping; Interleukin-2 - biosynthesis; Killer Cells, Natural - immunology; Male; Medical sciences; Neoplasms, Experimental - immunology; Oxonic Acid - pharmacology; Pharmacology. Drug treatments; Pyridines - pharmacology; Rats; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tegafur - pharmacology; Tumors
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-005-0150-0

S-1 is an oral formulation combining tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. We examined whether Oxo reduces the immunosuppression induced by 5-fluorouracil (5-FU) in the rat. The body weight of rats treated with S-1 (FT + CDHP + Oxo) for seven consecutive days was significantly higher than that of rats treated with a combination of FT plus CDHP (FT + CDHP) for a similar period. The number of peripheral leukocytes was significantly higher in the S-1-treated rats (S-1 group) than that in the FT + CDHP-treated rats (FT + CDHP group). There was no apparent difference between the two treated groups in phenotypic changes of CD3-, CD45-, CD4-, or CD8-positive cells from the spleen or mesenteric lymph nodes. However, the natural killer activities of both spleen cells and mesenteric lymph node cells were significantly higher in the S-1 group than in the FT + CDHP group. Interleukin (IL)-2 production by spleen cells stimulated with concanavalin A was significantly lower in the FT + CDHP group than in the S-1 group. Although IL-2 production by mesenteric lymph node cells in the S-1 group was lower than that in untreated rats, it was higher than that in the FT + CDHP group. These findings suggest that Oxo in S-1 may reduce the suppression of antitumor immunity induced by 5-FU.