Figure 5 from The Lysine Demethylase KDM4C Is an Oncogenic Driver and Regulates ERK Activity in KRAS-Mutant Pancreatic Ductal Adenocarcinoma

Pan-KDM4 Inhibitor TACH107 reduces proliferation and colony formation in PDAC cell lines in vitro and increases survival in vivo. A, MTT assay shows reduced proliferation in PDAC cell lines following TACH107 treatment, significance determined by one-way ANOVA. B, Reduced colony formation ability of human and mouse PDAC cell lines upon treatment with varying doses of TACH107 and (C) Quantification of the number of colonies, one-way ANOVA was used to assess significance. D, Survival plot showing B6 mice transplanted with PDAC cell line KPC-mT4 and treated with TACH107 survive longer than those treated with vehicle only (n = 3). E, Results from CETSA show increased heat stability of KDM4 proteins when treated with TACH107 vs. DMSO. F, Representative IF images showing increased H3K9me3 signal after TACH107 treatment compared with control cells. G, Normalized fluorescence intensity of H3K9me3 signal calculated by the corrected total cell fluorescence method using ImageJ, significance determined via unpaired Student t test. For all plots; * is P ≤ 0.05; ** is P ≤ 0.01; *** is P ≤ 0.001; and **** is P ≤ 0.0001. H, Representative micrographs showing H3K9me3 levels by IHC in PDAC tumors harvested on day 30 from mice injected with PDAC cell line KPC-mT4 demonstrate increased H3K9me3 mark in the TACH107 treated mice compared with vehicle control mice. Scale bar, 100 μm. I, Quantification of the area of positive staining in H using ImageJ color deconvolution plugin for IHC DAB staining, the difference between vehicle-treated and TACH107-treated samples is statistically significant.