Synergistic antitumor effects of rat gamma-interferon and human tumor necrosis factor alpha against androgen-dependent and -independent rat prostatic tumors.

We have examined the antitumor effects of rat gamma-interferon (IFN-gamma) and human tumor necrosis factor alpha (TNF) against androgen-dependent and -independent Dunning rat prostatic tumors. In vitro studies, using the double layer soft agar assay, showed a very limited antiproliferative activity of the drugs in the dose range tested (1-1000 units IFN-gamma and/or 1-1000 ng TNF/dish). For in vivo studies IFN-gamma and TNF were administered s.c., peritumorally. IFN-gamma was given 3 times/week, 8,000 or 80,000 units/rat, and TNF 5 times/week, 10 or 100 micrograms/rat. IFN-gamma and TNF monotherapy were not significantly effective in inhibiting tumor growth, except for IFN-gamma against the androgen-independent MatLyLu tumor. Combinations of IFN-gamma and TNF had synergistic antiproliferative effects against all four tumor lines tested; however, complete growth inhibitions could not be achieved. Survival studies showed significant increase in survival of tumor-bearing rats.