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.