Long-term effect of tumor necrosis factor and gamma interferon in human pancreatic carcinoma cells

The long-term cytotoxic/cytostatic effects of recombinant human tumor necrosis factor alpha (rhTNF) and gamma interferon (rhIFN-gamma) were studied in five human pancreatic carcinoma cell lines. The pancreatic tumor cell lines were heterogenous in their response to individual cytokines. During a 7-d incubation, MIA PaCa-2 cells were more sensitive to rhTNF than rhIFN-gamma, whereas ASPC-1, T3M4, and COLO 357 cells were more sensitive to rhIFN-gamma than rhTNF. PANC-1 cells were relatively insensitive to both cytokines. In a previous report, we demonstrated synergistic cytotoxic effects of rhTNF and rhIFN-gamma during 48-h incubations in ASPC-1 and COLO 357 cells (Raitano et al, Pancreas, April, 1990). In this study, a 7-d treatment with both rhTNF and rhIFN-gamma did not produce synergistic effects in any of the cell lines. However, a 24-h treatment with rhIFN-gamma, followed by removal of the cytokine, markedly increased the long-term cytotoxic/cytostatic effects of rhTNF in ASPC-1, COLO 357, and T3M4 cells. In contrast, a similar pretreatment with rhTNF did not increase the long-term cytotoxic/cytostatic effects of rhIFN-gamma in any of the cell lines. These data suggest that, in some human pancreatic carcinoma cell lines, rhIFN-gamma may be especially useful in the long-term suppression of growth. Furthermore, brief pulses of rhIFN-gamma may also be especially efficacious when followed by a subsequent prolonged exposure of cells to rhTNF.