The modulating effect of interferon alpha-2a on the antitumor activity of UFT against a human gastric carcinoma xenograft, SC-1-NU, in nude mice.
The modulating effect of recombinant human interferon alpha-2a (IFN) on the antitumor activity of UFT, a mixed compound of tegafur and uracil at a molar ratio of 1:4, was investigated against SC-1-NU, a human gastric cancer xenograft serially transplanted in nude mice. IFN was administered subcutaneously at a dose of 60,000 IU/mouse daily for 14 days, and UFT was given at a dose of 15 mg/kg as tegafur daily, except on Sundays, for 3 weeks. The agents were administered either alone or simultaneously. Synergistic antitumor activity on SC-1-NU was produced by the combination of IFN and UFT without any increment of side effects, and the combination therapy also increased intratumoral thymidylate synthetase (TS) inhibition and the amount of 5-fluorouracil (5-FU) in the intratumoral RNA. Thus, IFN seems to modulate the antitumor activity of UFT against SC-1-NU through an inhibition of DNA synthesis and RNA distortion, and therefore this combination could be useful for clinical application.
Kubota
T
T
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kurihara
N
N
Kase
S
S
Watanabe
M
M
Kumai
K
K
Kitajima
M
M
Inada
T
T
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D003131:Combined Modality Therapy; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012334:RNA, Neoplasm / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000473:pathology*; D005641:Tegafur / Q000494:pharmacology; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D014183:Transplantation, Heterologous; D014498:Uracil / Q000494:pharmacology
D004338:Drug Combinations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D013940:Thymidylate Synthase