Synergistic Effects of Vinblastine and Recombinant Interferon-β on Renal Tumor Cell Lines

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Abstract
Potential synergistic interactions between vinblastine (VBL) and recombinant interferon-.beta. (rIFN-.beta.) were assessed using median effect analysis. Calculation of the combination index demonstrated values less than 1 (indicating synergy) over a wide range of drug-induced growth inhibition for each of four different renal carcinoma cell lines (RCC). The degree of synergy observed could not be predicted from the morphology, doubling time, or relative sensitivity of the RCC lines to VBL and rIFN-.beta.. The optimal ratio of VBL to rIFN-.beta. in the combination appeared to be close to the ratio of the concentrations of each agent which yielded a 50% inhibition of growth. Although simultaneous presence of VBL and rIFN-.beta. in the culture medium was not required to demonstrate a synergistic effect, the minimum exposure time for rIFn-.beta. was determined to be 7 days. The uptake but not the egress of tritiated VBL into RCC cells was enhanced after growth for 4 days in 2.25 mg/ml of rIFN-.beta.. Median effect analysis can be shown to be independent of the mechanism of action of VBL and rIFN-.beta. and gives an indication of potential synergistic interactions over a wide range of drug effects. This method may prove useful in the selection of combinations of IFNs and antitumor drugs for clinical study.