(A-F) Isobolographic analysis of interactions between HDIs and CDDP.

<p>Isobolograms showing additive interactions between cisplatin (CDDP), suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) with respect to their anti-proliferative effects on three cancer cell lines (MCF7, T47D and MDA-MB-231) measured <i>in vitro</i> by the MTT assay. The median inhibitory concentrations (IC₅₀) for CDDP, SAHA and VPA are plotted graphically on the X- and Y-axes, respectively. The solid lines on the X and Y axes represent the S.E.M. for the IC₅₀ values for the studied drugs administered alone. The lower and upper isoboles of additivity represent the curves connecting the IC₅₀ values for CDDP and SAHA or VPA administered alone. The dotted line starting from the point (0, 0) corresponds to the fixed-ratio of 1:1 for the combination of CDDP with SAHA or VPA. The diagonal dashed line connects the IC₅₀ for CDDP and SAHA or VPA on the X- and Y-axes. The points A’ and A” depict the theoretically calculated IC_{50 add} values for both, lower and upper isoboles of additivity. The point M represents the experimentally-derived IC_{50 mix} value for total dose of the mixture expressed as proportions of CDDP and SAHA or VPA that produced a 50% anti-proliferative effect (50% isobole) in three cancer cell lines (MCF7, T47D and MDA-MB-231) measured <i>in vitro</i> by the MTT assay. On the graph, the S.E.M. values are presented as horizontal and vertical error bars for every IC₅₀ value. The experimentally-derived IC_{50 mix} value is placed close to the point A”, indicating additive interaction between CDDP and SAHA or VPA in three cancer cell lines (MCF7, T47D and MDA-MB-231) measured in vitro by the MTT assay.