EFFECT OF VALPROIC ACID ON INCREASING RADIOSENSITIVITY IN ANAPLASTIC THYROID CANCER CELL

PERONA M ; GRISSI C; DURÁN H; IBAÑEZ IL; CREMASCHI GA; JUVENAL GJ ; ROSEMBLIT C; PISAREV MA

Mar del Plata

Congreso; Reunión Anual de Biociencia 2019; 2019

Introduction: Histone deacetylase inhibitors (HDACi) have emerged recently as promising anticancer agents targeting histone and nonhistone proteins. Many studies show as well that HDACi are effective radiosensitizers in various types of malignancies. Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy. Radiotherapy (RT) is one of the main modalities of treatment for ATC. RT either as altered fractionation or in combination with chemotherapy has an important role in achieving local control. Objectives: Our purpose was to study the combined effect of the HDACi, valproic acid (VA), and ionizing radiation in an anaplastic thyroid cancer cell line (8505c). Methods: Cell viability was evaluated by MTT assay. Cells were pretreated with 1 mM VA and gamma irradiated at different doses. Radiation response was analyzed by clonogenic assay. Cell cycle and cell death were measured 24 and 48 h after irradiation. The microARN (miRNA) expression profile was also evaluated. Results: VA radiosensitized cancer cells as evidenced by the reduction of survival fraction at 2 Gy from 58.4 ± 2.1 to 37.9 ± 2.6 in the treated cells (p