Anti-proliferative and cytokinetic effects of tumor necrosis factor-alpha, interferon-alpha and 5-fluorouracil on a human tumor xenograft.
We have previously reported that interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha) blocked the cell cycle progression of cancer cells at the S to G2 transition, causing a synergistic antitumor effect. In this study, the combined effects of both these cytokines and 5-fluorouracil (FUra) on tumor growth and cell cycle progression were investigated in a human colon cancer cell line, RPMI 4788, transplanted in CD-1 nude mice. Daily administration of IFN-alpha and TNF-alpha for 21 days markedly suppressed the tumor growth and induced cytokinetic alterations in which S phase cells were increased and cells in G2/M phase were decreased. FUra added to these cytokines further suppressed tumor development but did not affect the cytokinetics further. Combination of FUra and cytokines in a low dose, either of which alone had no effect, suppressed the tumor growth. These findings demonstrate that IFN-alpha, TNF-alpha and FUra have a distinct antitumor effect in combination.
Tanaka
N
N
First Department of Surgery, Okayama University Medical School, Japan.
Kojima
K
K
Muro
M
M
Naomoto
Y
Y
Moreira
L F
LF
Orita
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D005472:Fluorouracil