Fig. 5: EI-52 inhibits tumor growth in mouse tumor models and induces cell death of patient-derived tumoroids and ex-vivo tumors.

A C57BL/6 mice (n = 9/group) injected subcutaneously with Lewis Lung Carcinoma cells were treated daily by intraperitoneal injection with vehicle (PBS, 40% PEG 400, 20% DMSO) or with 25 or 50 mg/kg of EI-52. Tumor volume was measured twice a week with an electronic caliper. B Five-week-old K-ras^LA2 mice (WT n = 5, K-Ras mutant n = 7) were treated intraperitoneally 5 times a week for 10 weeks with 25 mg/kg of EI-52. Tumor load was evaluated on a Perkin Elmer Quantum FX microCT scan. Left panel: example of image reconstitution of lungs from 2 mice treated for 10 weeks with vehicle or with EI-52. Right panel: tumor load in the lungs of vehicle- or EI-52-treated mice at 10 weeks. Statistical analysis was performed using a two-tailed Mann-Withney test; *p = 0.0177 (95% confidence interval). C Patient-derived cancer tumoroids from colon (male, age 77) and lung (female, age 64) were treated for 48 h with DMSO or indicated concentrations of EI-52. Cell death (PI-positive) and apoptosis (caspase 3/7 cleavage) were observed by OPERA imaging. Shown are two of three independent experiments. D Thick (250 μm) sections of surgical pieces from head and neck cancer patients (3 females and 8 males, age 54–82) were cultured in optimized medium in presence of DMSO or EI-52 (8 μM). 24 h later, thin sections were sliced and stained for the apoptotic marker cleaved-PARP (left panel). IHC scoring allows a semi-quantitative analysis of apoptosis (right panel). Mean score ± SEM from 11 samples, statistical analysis was performed using a two-tailed Wilcoxon t-test; *p < 0.0469 (95% confidence interval). Source data are provided as a Source Data file.