Fig 3. Effects of combined 5-FU and ornithine decarboxylase inhibitor DFMO on colon carcinoma cells.

HCT116 colon cancer cells were treated with 5-FU at 2.5 μM (IC₂₅ for wt-p53 line) or 15 μM (IC₂₅ for p53-null line) in combination with increasing doses of DFMO (simultaneous or one drug following the other). Cell viability at the 96-h end point was measured with MTS assay. A, dose-response curves. The straight line at around 70% viability shows the effect by 5-FU alone. The four curves represent different regimens: ●, DFMO alone; ▲, 5-FU + DFMO (simultaneous treatment for 48 h and drug-free medium for 48 h); ■, DFMO (48 h) then 5-FU (48 h); ○, 5-FU (48 h) then DFMO (48 h). No combination (simultaneous treatment, DFMO post-treatment, or DFMO pre-treatment) produced synergistic cytotoxicity. Some pre-treatment and post-treatment regiments of DFMO are antagonistic to 5-FU depending on the p53 status. DFMO post-treatment and DFMO pre-treatment had the strongest antagonistic effects in wt-p53 and p53-null lines, respectively. B, analysis of the combination effect of 5-FU and DFMO using the Chou and Talalay CI. Dose-response interactions between 5-FU and DFMO were expressed as a CI value (CI < 1: synergism, CI = 1: additivity, CI > 1: antagonism). Simultaneous treatment with 5-FU and DFMO only had additive effects in most regimens. 5-FU followed by DFMO had a strong antagonistic effect in the wt-p53 cells and DFMO followed by 5-FU had a strong antagonistic effect in the p53-null cells.