The anti-tumor effects of actinomycin D (Act D) and recombinant human tumor necrosis factor (TNF)-α have been studied on 4 established murine tumor cell lines: MmB16 melanoma, Lewis lung (LL/2) carcinoma, LI sarcoma and LI210 leukemia. During short-term incubation (24 hr) Act D produced dose-dependent cytostatic/cytotoxic effects against MmB16, LL/2 and LI tumor cells but did not reduce the viability of these cells even at high concentration (10 μg/ml), below a threshold of 30-60%. However, LI210 leukemic cells were highly susceptible to Act D, and no viable cells were detected in cultures incubated with I μg/ml of Act D. TNF-α alone, when used under the same culture conditions, had only a negligible effect on all cell lines tested. However, the combination of this cytokine with Act D produced synergistic cytotoxic effects against MmB16, LL/2 and LI cells but not against LI21O leukemia cells, in an in vivo model of regional therapy in which tumor-bearing mice were treated with Act D and TNF-α, a correlation with in vitro results was observed. In mice bearing MmB16 melanoma, LL/2 carcinoma and LI sarcoma, the most potent anti-tumor effects were observed in mice treated with Act D and TNF-α together. This treatment led to a delay of tumor growth and induced complete tumor regression in some cases. On the contrary, TNF-α did not enhance the effect of Act D in mice injected with LI210 leukemia cells. Our results show that TNF-α can potentiate the anti-tumor effects of Act D against tumors weakly susceptible to Act D and may be a useful adjuvant to chemotherapy in the local treatment of neoplasia.
|Original language||English (US)|
|Number of pages||6|
|Journal||International Journal of Cancer|
|State||Published - May 3 1996|
ASJC Scopus subject areas
- Cancer Research