ezh2 inhibitors  (TargetMol)

Journal: Scientific Reports

Article Title: Investigating the oncogenic role of aberrant EZH2 in hepatoblastoma

doi: 10.1038/s41598-026-38038-0

Figure Lengend Snippet: Tumors with embryonal histology have features of cycling Hep T cell cluster. a . EZH2 is elevated in HB tumor though to varying degree based on histologic subtype. PRC2 components, SUZ12 and EED are often upregulated compared to normal adjacent liver, but protein expression patterns are not consistent. b . Gene expression was analyzed in tumor grouped by histologic subtype to look at PRC2 genes, tumor markers, and genes regulated by EZH2. EZH2 gene expression is highest in embryonal subtypes, as well as AURKB, Ki67, and GPC3. Fetal histology had the highest level of SUZ12 and CTNNB1 expression, where EED gene expression did not show elevation by subtype. Tumors with mixed epithelial histology had muted expression levels making interpretation difficult. (N = 33 liver, N = 25 tumor stratified by histology).

Article Snippet: In vitro cells were treated with EZH2 inhibitors (tazemetostat (EPZ-6438) 10 μM -Selleck, GSK126 5 μM, Tocris) for 72 h. Cisplatin (0-400 μM) was then administered for 24 h. HepG2 (RRID:CVCL_0027) cells (passage 5–25) were purchased from ATCC and not authenticated.

Techniques: Expressing, Gene Expression

Journal: Scientific Reports

Article Title: Investigating the oncogenic role of aberrant EZH2 in hepatoblastoma

doi: 10.1038/s41598-026-38038-0

Figure Lengend Snippet: Complex regulation through canonical and noncanonical mechanisms. a . Gene expression analysis of paired liver and HB tumor samples demonstrated upregulation of EZH2, AURKB, CTNNB1, and TGFβ. EED and SUZ12 are also upregulated though not significantly. MYC, CCND1, STAT3, and CDH1 are downregulated in tumor compared to liver. b . EZH2 protein expression in tumor is not in stoichiometric relationship with other PRC2 components. EZH2 and EED are observed in the nucleus. EZH2 expression is also observed in mitotic cells from HB tumor, where SUZ12 expression is highest in the cytoplasm. c . Paired patient liver and HB tumor gene expression was compared and demonstrated significant upregulation of EZH2 in HB. Slight upregulation was also seen in PRC2 components, SUZ12 and EED, with correlation between these genes in paired samples but inconsistent upregulation. d . EZH2 positive, mitotic cells are significantly increased in HB cells compared to normal human hepatocytes. This expression pattern is also elevated in HB patient derived cells compared to HepG2 cells, though not all HB cells show a statistical significance increase compared to HepG2.​(N = 22 pairs, paired patient tumor and liver).

Article Snippet: In vitro cells were treated with EZH2 inhibitors (tazemetostat (EPZ-6438) 10 μM -Selleck, GSK126 5 μM, Tocris) for 72 h. Cisplatin (0-400 μM) was then administered for 24 h. HepG2 (RRID:CVCL_0027) cells (passage 5–25) were purchased from ATCC and not authenticated.

Techniques: Gene Expression, Expressing, Derivative Assay

Journal: Scientific Reports

Article Title: Investigating the oncogenic role of aberrant EZH2 in hepatoblastoma

doi: 10.1038/s41598-026-38038-0

Figure Lengend Snippet: EZH2 inhibition makes HB cells more sensitive to Cisplatin treatment. a . Liver cancer cells treated with EZH2 inhibitors in vitro followed by cisplatin demonstrated differential response to treatment. HCN-NOS showed no response to EZH2 inhibitors alone (HBc108). HB cells, HUH6 and HBc130 showed improved response to cisplatin in combination with EZH2 inhibition, with variability between the inhibitors. HepG2 cells showed elevated cisplatin resistance but better response with EZH2 inhibition. HBc129 showed limited response to cisplatin and no added benefit of EZH2 inhibition, while HUH7, HCC cells showed better cisplatin response but no additive effect with EZH2 inhibitors. b . Cell morphology suggests improved cell death and synergy between EZH2 inhibitors and cisplatin treatment. (Images represent EZH2 inhibitors added for 24 h, then 400 μM cisplatin plus inhibitors for an additional 24 h – 20X images with trypan blue to highlight remaining dead cells.) (Cell lines represent 6 technical replicates, with biological triplicates for all experiments).

Article Snippet: In vitro cells were treated with EZH2 inhibitors (tazemetostat (EPZ-6438) 10 μM -Selleck, GSK126 5 μM, Tocris) for 72 h. Cisplatin (0-400 μM) was then administered for 24 h. HepG2 (RRID:CVCL_0027) cells (passage 5–25) were purchased from ATCC and not authenticated.

Techniques: Inhibition, In Vitro

Journal: Scientific Reports

Article Title: Investigating the oncogenic role of aberrant EZH2 in hepatoblastoma

doi: 10.1038/s41598-026-38038-0

Figure Lengend Snippet: EZH2 inhibition improves in vivo tumor response to cisplatin in HB PDX model. HB66 PDX model was pretreated with 150 mg/kg EPZ-6438 5 times per week. 5 mg/kg cisplatin was then started and EPZ-6438 continued to study termination. a . MRI images show tumor volume at initiation of treatment and at 2 weeks of treatment. b . Reduction of H3K27me 3 is shown following EPZ-6438 and cisplatin treatments alone, but enhanced, synergistic reduction is seen after combination treatment with EPZ-6438. c . When comparing tumor volume, cisplatin alone showed modest reduction in tumor growth, while EPZ-6438 and cisplatin plus EPZ-6438 showed even greater reduction in overall tumor growth, supportive of in vitro studies. (one PDX model, with biological duplicate or triplicate per condition).

Article Snippet: In vitro cells were treated with EZH2 inhibitors (tazemetostat (EPZ-6438) 10 μM -Selleck, GSK126 5 μM, Tocris) for 72 h. Cisplatin (0-400 μM) was then administered for 24 h. HepG2 (RRID:CVCL_0027) cells (passage 5–25) were purchased from ATCC and not authenticated.

Techniques: Inhibition, In Vivo, In Vitro

Journal: Scientific Reports

Article Title: Investigating the oncogenic role of aberrant EZH2 in hepatoblastoma

doi: 10.1038/s41598-026-38038-0

Figure Lengend Snippet: Qualitative next generation sequencing using CinCseq cancer panel to define genetic sequence variants. a . 11 patient tumors were sequenced from FFPE tissue to explore clinically relevant variants as well as VUS. EZH2 and SUZ12 have VUS in 11 out of 11 samples and EED in 9 out of 11. As expected, CTNNB1 variants are observed in 9 out of 11 patients. STAT3 variants are also observed but at a lower frequency. Other less frequently observed variants are also displayed. b . Schematic gene map drawings to represent the location of detected VUS in EZH2 and SUZ12 (all exons not shown).

Article Snippet: In vitro cells were treated with EZH2 inhibitors (tazemetostat (EPZ-6438) 10 μM -Selleck, GSK126 5 μM, Tocris) for 72 h. Cisplatin (0-400 μM) was then administered for 24 h. HepG2 (RRID:CVCL_0027) cells (passage 5–25) were purchased from ATCC and not authenticated.

Techniques: Next-Generation Sequencing, Sequencing