Action of thyroid hormones in sorafenib treatment of thyroid cancer

MATEO N CAMPOS HAEDO; DIAZ FALQUE MC; STERLE HA; JOHANNA A DÍAZ ALBUJA; PERONA M; JUVENAL GJ; CREMASCHI GA; ROSEMBLIT C

Mar del Plata

Congreso; Reunion Anual de Sociedades de Biociencias SAIC SAI FAIC SAFIS; 2022

Sociedad Argentina de Investigaciones Clínicas

Action of thyroid hormones in sorafenib treatment of thyroid cancerCampos Haedo MN1, Diaz Flaqué MC1, Sterle HA1, Díaz Albuja JA1, MN, Perona M2,3, Juvenal GJ2,3, Cremaschi GA1, Rosemblit C1.1 BIOMED UCA-CONICET, Buenos Aires, Argentina.2 Departamento de Radiobiología (CAC), Comisión Nacional de Energía Atómica (CNEA), Buenos Aires, Argentina.3 Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.Background. Thyroid carcinoma (TC) is the most common endocrine neoplasia. Its incidence has increased in the last 40 years worldwide. Sorafenib (Sor), a tyrosine kinase inhibitor, was approved for the treatment of TC, being hypothyroidism the most frequent consequence of Sor-induced endocrine dysfunction. We have described that thyroid hormones (TH) increase cell proliferation in TC lines. Thus, hormone replacement therapy to treat Sor-induced hypothyroidism could negatively affect the antitumor action. We have also shown that the selective inhibition of the TH membrane receptor, αVβ3 integrin, diminishes proliferation. Objective. To study integrin αVβ3 inhibition to enhance Sor antineoplastic activity in TC and the molecular mechanisms involved. Results. We first studied the role of αvβ3 integrin in Sor inhibition of TH-induced proliferation in TC cells. The treatment of the human anaplastic 8505C TC cells with the αvβ3 integrin antagonist cilengitide (Cile) inhibits TH-induced proliferation by MTS assay (p