Enhanced inhibition of colony formation of human renal cell carcinoma in soft agar by the combination of alpha-difluoromethylornithine and recombinant gamma-interferon

Abstract

We studied the inhibitory activity of alpha-difluoromethylornithine (DFMO) and alpha-, recombinant beta-, and recombinant-gamma-interferons (alpha-, rec-beta-, and rec-gamma-IFNs) on in vitro growth of 3 established human urogenital tumors (KO-RCC-1 from renal cell carcinoma, Bewo from choriocarcinoma of the uterus, and HT-1197 from transitional cell carcinoma of the urinary bladder) and 16 primary renal cell carcinomas obtained by nephrectomy. Treatment with DFMO together with rec-IFN-gamma synergistically inhibited KO-RCC-1 cell growth in monolayer culture and in soft agar. The other two established cell lines were less susceptible to this treatment. Combination of DFMO and rec-IFN-gamma was more inhibitory than that of DFMO and either IFN-alpha or rec-IFN-beta. The polyamine content in KO-RCC-1 cells was decreased to a greater extent by combined treatment with DFMO and rec-IFN-gamma than that in Bewo and HT-1197 cells. The effect of these agents in 11 of the 16 primary renal cell carcinomas, which could show clonal growth in double layer soft agar, was examined. More than 50% inhibition of colony growth was seen in only one case (9%) treated with 5 mM DFMO alone and in 2 cases (18%) treated with rec-IFN-gamma alone (1,000 units/ml) but in 10 of the 11 cases (91%) with the combined treatment. Our results indicate that combined treatment with DFMO and rec-IFN-gamma can be more effective than that with either agent individually in inhibiting cell growth of human renal cell carcinoma in vitro.