Fig. 1: Manidipine-2HCl sensitizes colorectal cancer cells to BCL-XL inhibition.

a Matrix titration and corresponding Bliss synergy scores of the Manidipine-2HCl and A-1155463 in Co01. Cell viability was measured by CellTiter Blue (n = 4). Relative inhibition on viability was plotted and Bliss synergy scores were calculated; b Representative plots of Annexin V and PI FACS upon treatment with or without 2 µM Manidipine-2HCl and/or 5nM A-1155463 after 48 h, determined by flow cytometry. n = 4; Percentage of Co01 cells showing caspase-3 activity (c) or PI positivity (d) upon treatment with or without 2 µM Manidipine-2HCl and/or 5nM A-1155463 after 48 h, determined by flow cytometry. n = 4; Matrix titration and corresponding Bliss synergy scores of Manidipine-2HCl and A-1155463 treatment of patient-derived tumor organoids p9T(e) and p16T (f). Cell viability was measured by CellTiter Blue (n = 4). Relative inhibition of viability was plotted and Bliss synergy scores were calculated; g Matrix titration and corresponding Bliss synergy scores of Manidipine-2HCl and A-1155463 treatment in healthy human platelets.1 μM A-1155463 was used as positive control for platelet killing. Viability was determined by CellTiter Blue (n = 3). Relative inhibition of viability was plotted and the Bliss synergy scores were calculated. h Matrix titration and corresponding Bliss synergy scores of Manidipine-2HCl and A-1155463 treatment in human normal colon organoids. Viability was determined by CellTiter Glow (n = 3). Relative inhibition on viability was plotted and Bliss synergy scores were calculated. Significance was calculated with Mann–Whitney test; ns: not significant. ∗p ≤ 0.05.