Potassium oxonate, an enzyme inhibitor compounded in S-1, reduces the suppression of antitumor immunity induced by 5-fluorouracil.
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.
Yamashita
Tetsuro
T
Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, 602-8566 Kyoto, Japan.
Ueda
Yuji
Y
Fuji
Nobuaki
N
Itoh
Tsuyoshi
T
Kurioka
Hideaki
H
Shirasaka
Tetsuhiko
T
Yamagishi
Hisakazu
H
D000818:Animals; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005472:Fluorouracil / Q000037:antagonists & inhibitors*; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D009374:Neoplasms, Experimental / Q000276:immunology*; D010094:Oxonic Acid / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D005641:Tegafur / Q000494:pharmacology*
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; C489337:potassium oxonate; D010094:Oxonic Acid; D005472:Fluorouracil