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 and BCL2 inhibition on cellular proliferation were determined by 3D-colony formation assay using Matrigel. Lentiviral particles carrying pLX304-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.
Authors and affiliations
N.R. Fatkhutdinov(1, 2), R. Zhang(2), R.G. Kiyamova(3) 1-Kazan Federal University, Kremlevskaya st., 18, Kazan, 420008, Russian Federation; 2-The Wistar Institute, Philadelphia, USA, PA 19104, 3601 Spruce st. 3-Research Laboratory «Biomarker», Department of Biochemistry, Biotechnology and Pharmacology, Institute of Fundamental Medicine and Biology of Kazan Federal University, Kremlevskaya st., 18, Kazan, 420008, Russian Federation E-mail: nrfatkhutdinov@gmail.com
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