PhD Scientific Days 2026

Poster Session 1.D - Pathological and Oncological Sciences

Pharmacological degradation of EZH2 effectively inhibits cell growth and affects metabolic plasticity in grade 3 meningioma cell lines

Előadó neve

Dr. Szőke, Péter

Neptune code

JAMQE2

Előadó munkahelye

Department of Pathology and Experimental Cancer Research

Előadó telefonszáma

+36205872626

Előadó e-mail címe

szokepeter1229@gmail.com

Az előadás címe

Pharmacological degradation of EZH2 effectively inhibits cell growth and affects metabolic plasticity in grade 3 meningioma cell lines

Szerző(k) neve és munkahelye

Péter Szőke¹, Dániel Sztankovics¹, Ágnes Márk¹, Anna Sebestyén¹, Katalin Dezső¹, Bálint Scheich¹

1: Department of Pathology and Experimental Cancer Research

Bemutatás módja

Poszter

Szekció

Poster Session 1.D - Pathological and Oncological Sciences

Language of the presentation

Hungarian

Preferred session

Pathological and Oncological Sciences

Összefoglaló szövege

Introduction: Anaplastic (CNS WHO grade 3) meningiomas are aggressive tumors of the
meninges, for whom effective systemic treatment options are currently not available. Recent studies indicate a pivotal role of epigenetic dysregulation in their pathogenesis, including the overactivation of the Polycomb Repressive Complex 2 (PRC2) and its catalytic subunit, Enhancer of Zeste Homolog 2 (EZH2). Metabolic plasticity also appears to be an emerging pathogenetic mechanism that is also a promising therapeutic target.
Aim: Our aim was to evaluate the in vitro efficacy of the EZH2-selective degrader MS-1943
in human meningioma cell lines IOMM-Lee and BEN-MEN-1.
Methods: Effects of MS-1943 on IOMM-Lee and BEN-MEN-1 cell growth was characterized using the Alamar blue and sulforhodamine-B tests. Changes in the cell cycle and cell death were analyzed using flow cytometry. Protein expression changes, including alterations of key metabolic enzyme expressions, were evaluated with WES Simple capillary immunoassay.
Results: MS-1943 demonstrated significant, concentration-dependent growth-inhibitory
effects at the 1.25–5 µM range, more potently in IOMM-Lee cells. In the IOMM-Lee cell line
MS-1943 triggered a modest cell cycle arrest (G0/G1 phase) and also induced cell death (both necrotic and apoptotic). MS-1943 increased p21 expression in both cell lines, and also increased p53 and decreased FOXM1 expression in IOMM-Lee cells. Furthermore, MS-1943 reduced LDHA expression and LDHA/LDHB ratio in IOMM-Lee cells, suggesting inhibited anaerobic glycolysis, while increased FASN expression (the key enzyme of fatty acid
synthesis) in BEN-MEN-1 cells.
Conclusion: The EZH2 selective degrader MS-1943 demonstrates potent in vitro efficacy
against both IOMM-Lee and BEN-MEN-1 meningioma cell lines, while inducing divergent
alterations in metabolic plasticity. These findings suggest that non-conventional, histone methylation-independent functions of EZH2 play a fundamental role and maybe promising targets of potential future therapeutic approaches in these tumors.
Funding: National Research, Development and Innovation Office grant NKFIH-PD-146549.
National Research, Development and Innovation Office grant NKFIH-EKÖP-2025-503.

University

Semmelweis University

Supervisor

Bálint Scheich

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8033

Start

17:12

End

17:15