Fig. 1.
Enzalutamide and metformin in combination synergistically inhibit the growth of enzalutamide-resistant CRPC in vitro. Cell viability assay of isogenic CRPC lines treated with either enzalutamide (A, C, E) or metformin (B, D, F) to compare IC50 values. Data are scaled into percentages and normalized to untreated groups, then shown as mean ± SD (n = 3). Clonogenic assay of MR49F (G), C4–2R (H), and 22Rv1 (I) treated with DMSO as control or drugs indicated for up to 14 days. Quantification of relative colony number is indicated below where *P ≤ .05; **P ≤ .01; ***P ≤ .001. Synergy scores were calculated for 22Rv1 (J), C4–2R (K), and MR49F (L) after treatment with varying doses of the indicated drugs. Scores ≤ −10 indicate an antagonistic interaction, scores between −10 and 10 indicate an additive effect, and scores ≥10 are considered synergistic.