ROLE OF THYROID HORMONES IN BEXAROTENE- AND LAPATINIB-INDUCED MDR1 ACTIVITY IN TRIPLE NEGATIVE BREAST CANCER CELLS

DIAZ ALBUJA JA; ROSEMBLIT C; DEBERNARDI MM; CAYROL MF; STERLE HA; PAULAZO MA; CREMASCHI GA; DIAZ FLAQUE MC

Congreso; XVII Latin American Thyroid Society Congress; 2019

Chemoresistance is a major cause of cancer treatment failure. Many BC cells develop resistance to chemotherapy by diminishing intracellular drug accumulation, upregulating protein levels or activiting transporters like MDR1. Previously we demonstrated that Thyroid Hormones (THs) modulate chemotherapy response 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 dysfunction is recognized as an important side effect of such therapies, potentially manageable by THs administration. Objectives: Being MDR1 the major protein involved in the efflux of cytotoxic agents, the aim of this study was to evaluate Bexarotene- and Lapatinib-induced MDR1 activity in BC. Methods: MDA-MB-231 cells viability and proliferation was evaluated by Cell Titer Blue and trypan blue assay. MDR1 mRNA expression was evaluated by qPCR and activity was measured by Rho123 efflux assay. Results: We demonstrated that Bexarotene and Lapatinib inhibited MDA-MB-231 cells proliferation (p < 0,05) and THs increased cell viability (p < 0.01) and impaired the action of both drugs. On the other hand, Bexarotene and Lapatinib modulated MDR1 mRNA expression and protein levels. We also evaluated MDR1 activity and found that both Bexarotene and Lapatinib induced Rho123 exclusion. Conclusion: THs affect the action of Bexarotene and Lapatinib by mechanisms to be further unraveled that would include the participation of MDRs. Conflict of interest: None declared.