Influence of human leukocyte interferon (HuIFN-alpha/Le/) and cimetidine on the proliferation of cultured melanoma cells in vitro.

We have previously demonstrated the therapeutic efficacy of combined treatment with partially purified leukocyte interferon and cimetidine in patients with metastatic malignant melanoma. To study possible effector mechanisms behind this anti-tumor activity, the antiproliferative effect in vitro on two human melanoma cell lines by the two substances used singly or in combination was investigated. Both cell lines demonstrated a dose-dependent sensitivity to interferon. Over a concentration range of 10(-4) to 10(-7) M cimetidine did not exert an anti-proliferative effect, nor did it enhance the effect of interferon. Only at higher concentrations did cimetidine suppress the growth of one of the lines. These results suggest that the observed clinical effect is not mediated by an augmentation of a direct growth inhibitory effect of interferon by cimetidine.