Effect of tumor necrosis factor-alpha and interferon-gamma on the growth of human prostate cancer cell lines.

Human recombinant tumor necrosis factor-alpha (rTNF-alpha, 10(-12)-10(-8) M) inhibited the proliferation of androgen-dependent LNCaP cells by 32-56%. In contrast, proliferation of androgen-independent PC-3 and JCA-1 cells was only slightly inhibited, or not inhibited at all, respectively. Human recombinant interferon-gamma (rIFN-gamma, 500 U/ml) decreased proliferation of PC-3 and JCA-1 cells by 35% and 53%, respectively, but had no effect on LNCaP cells. Interestingly, the combination of rIFN-gamma and TNF-alpha had greater antiproliferative effects on JCA-1 cells than treatment with either cytokine alone. However, the antiproliferative effects of this combination were similar to those observed for PC-3 or LNCaP cells treated with rIFN-gamma or TNF-alpha alone, respectively. These data suggest that some forms of androgen-independent prostate cancer may benefit from a combination therapy of IFN-gamma and TNF-alpha, while the use of IFN-gamma alone may be more efficacious in others.