Combinations of interferon with platinum complexes: synergistic and antagonistic effects on growth inhibition of MCF-7 and MDA-MB231 breast cancer cells

The growth-inhibitory effects of combining interferons (IFN) with platinum(II) complexes were tested with the aim of comparing these in cultures of estrogen-receptor(ER)-negative MDA-MB₂₃₁ and ER-positive MCF-7 breast cancer cell lines. Another aim was to test whether IFN as a biological response modifier could enhance the effect of the Pt complexes in vitro in an attempt to find an explanation for their more potent antitumor effects in in vivo models. Here it is shown that in both cell lines the combinations of different IFN with all three Pt complexes generally resulted in additive growth inhibition, as calculated by the product of the fraction of surviving cells obtained with each compound alone. Moreover, in MCF-7 cells natural IFN (nIFN) combined with aqua[meso-1,2-bis-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]sulfatoplatinum(II) (meso-6-Pt) resulted in synergistic inhibition. This synergy could be attributed to the estrogenic property of meso-6-Pt, since the ligand and estradiol also enhanced the inhibitory effect of nIFN. In contrast, the combination of recombinant IFN and meso-6-Pt was antagonistic in MDA-MB₂₃₁ cells. These results show that, in spite of the similar responses of the ER-negative and ER-positive cells to each compound alone, these cells show unexpected differences in their sensitivity to combinations of IFN and the new Pt complex meso-6-Pt.Abbreviations ER estrogen receptor - IFN interferon(s) - nIFN natural interferon - rIFN recombinant interferon - meso-4-Pt aqua[meso-1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine]sulfatoplatinum(II) - meso-6-Pt aqua[meso-1,2-bis-(2,6-dichloro-4-hydroxyphenyl) ethylenediamine]sulfatoplatinum(II)