Fig. 3: ML264 restored oxaliplatin sensitivity in CRC PDOs by restoring the apoptotic response.

A Images of TUNEL (green) apoptosis detection in PDOs treated with oxaliplatin. Scale, 200 μm. B KLF5 (red) staining of PDOs treated with oxaliplatin at indicated concentrations. Scale, 200 μm. C Oxaliplatin significantly induced apoptosis in a dose-dependent manner. The proportion of KLF5+ cells significantly increased as the dose of oxaliplatin treatment increased (mean ± SD, n = 3 for each group, one-way ANOVA, *** p < 0.001). D, E The dose-response curves of combined treatment of ML264 and oxaliplatin. ML264 reduced the dose of oxaliplatin required to inhibit the growth of oxaliplatin-resistant CRC PDO. F, G Images of TUNEL (green) apoptosis detection in P2 and P6 treated as indicated. DNase I was used as a positive control. Scale, 200 μm. H ML264 restored oxaliplatin-induced apoptotic response in oxaliplatin-resistant CRC PDO (mean ± SD, n = 3 for each group, one-way ANOVA, *P < 0.05, **P < 0.01, *** p < 0.001). I, J The activity of caspase 3 (green) detection of P2 and P6. Ac-DEVD-CHO was used as a negative control. Scale, 200 μm. K ML264 restored oxaliplatin-induced activity of caspase 3 in oxaliplatin-resistant CRC PDO (mean ± SD, n = 3 for each group, one-way ANOVA, *P < 0.05, *** p < 0.001). The concentration of ML264 was 10 μM, and the concentration of oxaliplatin was 2 μM.