SYNERGISTIC INTERACTIONS BETWEEN INTERFERON-BETA AND CARBOPLATIN ON SK-MEL-28 HUMAN-MELANOMA CELL-GROWTH INHIBITION IN-VITRO

Carboplatin and interferon beta (IFN beta) were tested alone and in co mbination for their anti-proliferative activity on the human melanoma cell line SK-MEL 28 in vitro. Cells were incubated for 4 days in the p resence of carboplatin (0.1 mM and 0.1 mu M) and interferon beta (5 pM and 5 nM) and cell growth inhibition was determined by the sulphorhod amin B assay. The antiproliferative effects of the drug combinations w ere analyzed using Berenbaum's hyperplane theorem to determine additiv e, synergistic and antagonistic effects. IFN beta was found to be 10 0 00 times more active in inhibiting cell growth of SK-MEL 28 cells than carboplatin on the basis of IC50 values (IFN beta:IC50 = 1.24 nM, car boplatin:IC50 = 18.2 mu M). The addition of IFN beta at 0.5 nM reduced the IC50 value of carboplatin 18.0-fold; with IFN beta at 0.05 nM a d ose reduction of 1.84 was measured. At the carboplatin:IFN beta molar concentration ratios of 2000:1 and 6000:1, interaction indices (I) of 0.66 and 0.83 were determined respectively, indicating synergistic int eractions between the two drugs. At higher carboplatin:IFN beta molar ratios (20 000:1 and 60 000:1) an additive interaction was observed (I = 1.07 and 1.20). However, further in vitro studies with several mela noma cell lines are necessary to evaluate the potential effectiveness of the drug combination of carboplatin and IFN beta for eventual clini cal utilisation.