Fig. 3
From: Therapeutic targeting of BRCA1 and TP53 mutant breast cancer through mutant p53 reactivation
ZMC1 and its Zinc complex (Zn-1) improve the survival of BRCA1-deficeint mammary tumor bearing mice in a Trp53R175H allele specific fashion. a Bearing WAP-Cre;Brca1f/f;p53R172H/f mice were treated with either DMSO (ctrl, n = 9) or ZMC1 (2.5 mg/kg/d, n = 10). Kaplan-Meier survival curve (left panel) showed the overall survival of WAP-Cre;Brca1f/f;p53R172H/f mice with DMSO or ZMC1 treatment. The individual tumor growth was shown in the right panel. b Tumor-bearing WAP-Cre;Brca1f/f;Trp53f/f mice were treated with either DMSO (ctrl, n = 10) or ZMC1 (2.5 mg/kg/d, n = 9). Kaplan–Meier survival curve (left panel) showed the overall survival of WAP-Cre;Brca1f/f;p53f/f mice with DMSO or ZMC1 treatment. The individual tumor growth was shown in the right panel. c The chemical structure of Zn-1. d Tumor-bearing WAP-Cre;Brca1f/f;Trp53R172H/f mice were treated with DMSO (ctrl, n = 9) or Zn-1 (2.84 mg/kg/d, n = 7). Kaplan-Meier curve showed the overall survival of WAP-Cre;Brca1f/f;Trp53R172H/f mice with DMSO or Zn-1 treatment (left panel). The individual tumor growth was shown in the right panel. e The average log tumor volume of ZMC1 (n = 10) or Zn-1 (n = 7) treated WAP-Cre;Brca1f/f;Trp53R172H/f tumor-bearing mice versus post-injection time (in days). The fitted curves showed the log tumor volume of ZMC1 and Zn-1 treatment groups with the corresponding point-wise 84% confidence intervals (shaded bands). f Representative cleaved caspase-3 (CC3) staining in Brca1−/−;Trp53−/− and Brca1−/−;Trp53R172H/− tumors treated with either DMSO or ZMC1. g Quantification of CC3 in Brca1−/−;Trp53−/− and Brca1−/−;Trp53R172H/− tumors treated with either DMSO, ZMC1 or Zn-1 (three different tumors from three different tumor-bearing mice for each group). h Immunofluorescence staining of Ki67 in Brca1−/−;Trp53R172H/− tumors treated with DMSO (ctrl) or ZMC1. Scale bar: 50 µm
