THYROID HORMONE (TH) IMPACT ON THE PRO-LIFERATION OF ON HUMAN MELANOMA (ME) CELLS AND TREATMENT WITH THE SYNTHETIC REXINOID BEXAROTENE.

DEBERNARDI MM; CAYROL MF; ROSEMBLIT C; PROCOPIO C; CREMASCHI GA

Congreso; Reunion Conjunta de Sociedades de Biociencias 2020; 2020

With a constantly increasing worldwide incidence, melanoma (ME) represents the most lethal tumor among all skin cancers. Despite novel target therapies and immunotherapies improve overall survi-val rates, only a part of ME patients benefits from this therapies and others develops drug resistance, making crucial the study of new compounds for ME treatment.Bexarotene (Bex), an RXR agonist used for cutaneous T cell lym-phoma treatment, is currently being studied as alternative therapy for other types of cancer. The first aim of this work was to evaluate Bex effect on A375 and WM35 human melanoma cell lines in vitro. We found that Bex significantly decreases cell viability after 48h of both ME cell lines in a dose dependent manner (p<0.05). On the other side, Bex is associated with hypothyroidism so patients require the concomitant administration of a replacement therapy with the thyroid hormone (TH) levothyroxine. We previously found that TH, mostly through the action on integrin αVβ3, contribute to the malig-nant phenotype of T cell lymphomas and other tumor cells. In this sense, we then analyzed TH effect on the proliferation of ME cells and found that physiological levels of T3 and T4 (1nM and 100nM, respectively) induce 15 to 30% ME cell proliferation compare to con-trol (p<0.05). We then evaluated if the TH proliferative effect influen-ce Bex antineoplastic activity on ME cells. We treated cells with Bex for 48h with or without TH and found that Bex activity on cell viability was higher in the absence of TH (p<0.05). Importantly, we found in a skin cutaneous melanoma project from The Cancer Genome Atlas portal (TCGA-SKCM) that ME patients expresses RXR genes. We are now studying the inhibition of the TH membrane receptor, inte-grin αVβ3, as possible adjuvant for Bex antiproliferative actions on ME cells. Despite it should be studied more deeply, our preliminary results point Bex as a new therapeutic option that could be conside-red in the future for ME treatment.