Effect of Thyroid Hormones on the actions of oncology drugs in breast cancer cells.

CREMASCHI, GRACIELA A.; DIAZ ALBUJA, JOHANNA; DÍAZ FLAQUÉ, MARÍA CELESTE; CAYROL, FLORENCIA

Mar del Plata

Congreso; Reunion conjunta SAIC SAI SAFIS; 2018

Chemoresistance is a major cause of cancer treatment failure. Many breast cancer cells acquire multidrug resistance (MDR) by upregulating the level or activity of membrane protein such as Pgp, which enable the exclusion of cytotoxic substances from the intracellular environment. Previously we demonstrated that Thyroid Hormones (THs) modulate CYP3A4 expression and Doxorubicin chemosensitivity in T lymphoma cells. However, in breast cancer cells little is known about these mechanisms that lead to tumor chemotherapy resistance and are crucial to assure the success of treatment. Bexarotene and Lapatinib are recommended for breast cancer treatment but thyroid disfunction, is recognized as an important side effect of such therapies, potentially manageable by TH administration. Being MDR1 the major protein involved in the efflux of cytotoxic agents, we reasoned that Bexarotene- and Lapatinib-induced MDR1 activity may act as an important regulator in breast cancer MDR and that THs could modulate these effects. To this end, we first demonstrated that triple negative breast cancer MDA-MB-231 cells display both TR and integrin avb3 dimer (TH membrane receptor). Also, we demonstrate that Bexarotene and Lapatinib inhibits MDA-MB-231 cells proliferation (p