Effect of valproic acid on increasing radiosensitivity in anaplastic thyroid cancer cells

PERONA M; CREMASCHI GA; ROSEMBLIT C ; JUVENAL GJ; IBAÑEZ IL; DURAN H

Buenos Aires

Congreso; XVII Latin American Thyroid Society Congress; 2019

Latin American Thyroid Society

Background: Histone deacetylase (HDAC) inhibitors have emerged recently as promising anticancer agents. The antitumor activity of HDAC inhibitors has been linked to their ability to induce gene expression through acetylation of histone and nonhistone proteins. Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy. Radiotherapy (RT) is one of the main modalities of treatment for ATC. In most patients surgical resection is not possible. Therefore RT either as altered fractionation or in combination with chemotherapy has an important role in achieving local control. Objective: Our purpose was to study the combined effect of the HDAC inhibitor, valproic acid (VA), and ionizing irradiation in an anaplastic thyroid cancer cell line (8505c). Methods: Cell viability was evaluated by MTT assay. Radiation response was analyzed by clonogenic assay. Induction of apoptosis was identified by Hoechst staining. Gene and protein expression was measured by qPCR and Western blotting, respectively. Cells were incubated during 24 h with VA 1 mM (no effect on cell viability) for the following experiments. Results: VA radiosensitized cancer cells as evidenced by the reduction of survival fraction (p