Interferon alpha-2a shows antitumor activity in combination with 5-fluorouracil against human colon carcinoma xenografts: a study in reference to thymidylate synthetase activity inhibition.
To clarify the mode of antitumor activity shown by a combination of recombinant human interferon alpha-2a (IFN) and 5-fluorouracil (5-FU), experimental therapy was performed on human colon carcinoma (Co-4) xenografts serially transplanted into nude mice, using IFN and 5-FU, either alone or in combination. IFN alone showed dose-dependent antitumor activity and 5-FU also revealed a moderate antitumor effect. Although IFN, given as 600,000 units/mouse daily sc x 14, and 5-FU, given as 60 mg/kg q4d x 3 ip, showed additive antitumor activity against Co-4, the thymidylate synthetase (TS) inhibition rate was unchanged in the tumors treated with the IFN/5-FU combination in comparison with those treated with 5-FU alone. This suggests that the antitumor activity of IFN and 5-FU in combination does not involve augmentation of the TS inhibition by 5-FU.
Kubota
T
T
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Inada
T
T
Ogata
Y
Y
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage; D007370:Interferon Type I / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins; D013940:Thymidylate Synthase / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D011994:Recombinant Proteins; D013940:Thymidylate Synthase; D005472:Fluorouracil