Fig. 6

Targeting EZH2 mediated metabolic rewiring exhibits potential therapeutic efficacy in preclinical models of OC

(A) Colony formation assay in two primary OC cell lines derived from two OC patients (POVC17, POVC15). Cells were treated with DMSO, DZNep (1µM), YM281 (5µM), GSK126 (5µM) or EPZ-6438 (5µM) for 12 days. Growth medium was changed and inhibitors were also replenished every 3 days. Images are representative of three independent experiments unless stated otherwise

(B) Cell growth curve of two OC patient-derived primary tumor cell lines treated with DMSO, DZNep (1µM), YM281 (5µM) or GSK126 (5µM) for 96 h. Data are presented as the mean ± SD. ***P < 0.001

(C) Immunoblotting analysis of EZH2 and H3K27me3 levels in two OC patient-derived primary tumor cell lines upon EZH2 inhibitors treatment. Cells were treated with DMSO, DZNep (1µM), YM281 (5µM), GSK126 (5µM) or EPZ-6438 (5µM) for 72 h

(D) Tumor growth of PDX models in NOD-SCID mice treated with saline as control, EPZ-6438 at 200 mg/kg intragastrically daily, or DZNep at 1 mg/kg intraperitoneally twice a week (n = 6 per group). Data are presented as mean ± SD. ***P < 0.001(Two-way ANOVA with Tukey’s post hoc test)

(E) Bar graph showing the tumor weight on the 26th day post-treatment week (n = 6 per group). Data are presented as mean ± SD. **P < 0.01

(F) Body weight of each mouse post-treatment. Data are presented as mean ± SD.

(G) IHC analysis of EZH2, H3K27me3, IDH2 and Ki67 levels in the excised tumors from PDX models. Data are presented as mean ± SD. **P < 0.01, ***P < 0.001

(H) α-KG assay in PDX tumors upon EPZ6438 or DZNep treatment. Data are presented as mean ± SD. ***P < 0.001