The role of SWI/SNF chromatin remodeler composition in sensitivity to GSK126 and ABT263


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Abstract

Introduction. Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer characterized by frequent mutations in the ARID1A gene and low sensitivity to standard-of-care chemotherapeutic agents. The aim of the study. To determine the role of ARID1A in sensitivity of OCCCs to GSK126 and ABT263 Methods. ARID1A-mutant OCCC cell lines were used as study models. The effects of EZH2 andBCL2 inhibition on cellular proliferation were determined by 3D-colony formation assay using Matrigel. Lentiviral particles carryingpLX304-ARID1A vector were used for ARID1A restoration. Results. ARID1A-mutant OCCC cells are susceptible to EZH2 and BCL2 inhibition. Combination of ABT263 and GSK126 further decreases cellular proliferation. Sensitivity to aforementioned targeted therapies is dependent on ARID1A expression: restoration of wild type ARID1A in ARID1A-mutant OCCCs leads to the decrease in efficacy of EZH2 and BCL2 inhibitors. Conclusion. ARID1A is a key factor determining sensitivity of OCCCs to GSK126 and ABT263.

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About the authors

N. R Fatkhutdinov

Kazan Federal University; The Wistar Institute

Email: nrfatkhutdinov@gmail.com

R. Zhang

The Wistar Institute

R. G Kiyamova

Kazan Federal University

Research Laboratory «Biomarker», Department of Biochemistry, Biotechnology and Pharmacology, Institute of Fundamental Medicine and Biology

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