Fig. 2.

The synergistic antitumor activity of trabectedin and PARP inhibitors was cell line-dependent. FACS analysis of (a), DNA content (cell cycle distribution) after 48-h treatment with 0.125 nM trabectedin and 1.25 μM olaparib alone and their combination, green, yellow, and light blue represent G0/G1, S phase, and G2/M phase, respectively; as calculated by Flow Jo software; b apoptosis (Annexin V-PI staining) obtained after 72-h treatment with 0.125 nM trabectedin and 1.25 μM olaparib alone and their combination; c representative 7-day colony growth assay with 402.91 and SJSA-1 cells testing 0.125 nM trabectedin, 1.25 μM olaparib and their combination; d quantitation of three independent experiments of colony growth with 402.91 and SJSA-1 cells testing trabectedin, olaparib and their combination. e IC50 distribution of trabectedin as a single agent and in combination with olaparib or veliparib obtained by Calcusyn software after 72-h treatment with serial dilution of trabectedin (2–0.125 nM), olaparib (20–1.25 μM), veliparib (80–5 μM) as single agents or in constant combination with trabectedin, dashed lines indicate median IC50. Y error bars indicate mean ± S.E.M;*** p < 0.001 between combination and both single agents and controls