ANTIPROLIFERATIVE AND CYTOKINETIC EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA, INTERFERON-ALPHA AND 5-FLUOROURACIL ON A HUMAN TUMOR XENOGRAFT

We have previously reported that interferon-a (IFN-a) and tumor necros is factor-a (TNF-a) 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-fluoro uracil (FUra) on tumor growth and cell cycle progression were investig ated in a human colon cancer cell line, RPMI 4788, transplanted in CD- 1 nude mice. Daily administration of IFN-a and TNF-a for 21 days marke dly suppressed the tumor growth and induced cytokinetic alterations in which S phase cells were increased and cells in G2/M phase were decre ased. FUra added to these cytokines further suppressed tumor developme nt but did not affect the cytokinetics further. Combination of FUra an d cytokines in a low dose, either of which alone had no effect, suppre ssed the tumor growth. These findings demonstrate that IFN-a, TNF-a an d FUra have a distinct antitumor effect in combination.