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 combination for their antiproliferative activity on the human melanoma cell line SK-MEL 28 in vitro. Cells were incubated for 4 days in the presence of carboplatin (0.1 mM and 0.1 microM) and interferon beta (5 pM and 5 nM) and cell growth inhibition was determined by the sulphorhodamin B assay. The antiproliferative effects of the drug combinations were analysed using Berenbaum's hyperplane theorem to determine additive, synergistic and antagonistic effects. IFN beta was found to be 10,000 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, carboplatin: IC50 = 18.2 microM). 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 dose 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 interactions 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 melanoma cell lines are necessary to evaluate the potential effectiveness of the drug combination of carboplatin and IFN beta for eventual clinical utilisation.
Hübner
B
B
Institut für Pharmazie, Freien Universität Berlin, Germany.
Eckert
K
K
Garbe
C
C
Maurer
H R
HR
D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage / Q000494:pharmacology*; D008545:Melanoma / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016899:Interferon-beta; D016190:Carboplatin