Fig. 3: Genetic and pharmacological inhibition of SERPINE1 (PAI-1) reverses chemoresistance and metastasis in oxaliplatin-resistant HCT116 cells.

A Immunoblotting of PAI-1 in HCT116-MD and HD knocked down for the protein using two unique shRNAs (sh3 and sh5). B Fold change of PAI-1 protein in cell culture supernatant of HCT116-MD and HD knocked down for the protein relative to MD shRNA control (shCtrl). C Oxaliplatin IC50 fold change HCT116-MD and HD knocked down for the protein relative to MD shCtrl. Representative dose response curves of HCT116-MD shCtrl, PAI-1 sh3 and sh5 (D) and HCT116-HD shCtrl, PAI-1 sh3 and sh5 (E). F Three representative H&E staining for spontaneous metastasis in lung sections of mice harboring HCT116-PAR xenografts treated with oxaliplatin alone, or in combination with PAI-1 inhibitor, tiplaxtinin (20 mg/kg). F’ Quantification of tumor nodules area in lung sections of mice harboring HCT116-PAR xenografts treated with oxaliplatin alone, or in combination with tiplaxtinin (20 mg/kg). Statistical significance was determined using Ordinary one-way ANOVA followed by Sidak’s multiple comparisons test for (B, C) and two-tailed unpaired t-test for (F’).