Fig. 7

Combination therapy with irinotecan reverses EPI resistance by suppressing BLM lactylation and HR in pancancer PDX models. NSG mice were transplanted subcutaneously with NMIBC patient-derived xenografts (R-RT tumor tissues) and treated with EPI (2 mg/kg) and/or irinotecan (25 mg/kg) as indicated (n = 5); tumor images were acquired as shown in (a); tumor weights were measured (b), and volumes were calculated (c); one-way ANOVA followed by Tukey’s test. d Representative immunofluorescence images (left) and quantitative analyses (right) showing the nuclear expression and localization of γH2AX (green) colocalized with DAPI (blue) in PDX models; scale bar: 40 μm. e γH2AX expression and RAD51 chromatin accumulation were examined by western blot in PDX models. f Lactylated proteins were immunoprecipitated with anti-pan-Kla or IgG control in PDX models and analyzed by western blotting with anti-BLM. g, h Concentrations of ALT and AST in the serum of mice from different groups as indicated. NSG mice were transplanted subcutaneously with EPI-resistant breast cancer patient-derived xenografts and treated with EPI (2 mg/kg) and/or irinotecan (25 mg/kg) as indicated (n = 5); tumor images were acquired as shown in (i); tumor weights were measured (j), and volumes were calculated (k); one-way ANOVA followed by Tukey’s test. l γH2AX expression in whole-cell extracts and RAD51 accumulation in chromatin fractions were examined by western blot in PDX models. m Lactylated proteins were immunoprecipitated with anti-pan-Kla or IgG control in PDX models and analyzed via western blotting with anti-BLM. ***p < 0.001, **p < 0.01, *p < 0.05 represent significant differences between two groups; ns represents no significant difference