RESUMEN
Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive, carcinoma derived from follicular cells. While conventional treatments may improve patients' survival, the lethality remains high. Therefore, there is an urgent need for more effective ATC treatments. Cardiotonic steroids, such as ouabain, have been shown to have therapeutic potential in cancer treatment. Thus, we aimed to evaluate ouabain's effects in human anaplastic thyroid cells. For this, 8505C cells were cultured in the presence or absence of ouabain. Viability, cell death, cell cycle, colony formation and migratory ability were evaluated in ouabain-treated and control 8505C cells. The expression of differentiation and epithelial-to-mesenchymal transition (EMT) markers, as well as IL-6, TGFb1 and their respective receptors were also quantified in these same cells. Our results showed that ouabain in vitro decreased the number of viable 8505C cells, possibly due to an inhibition of proliferation. A reduction in migration was also observed in ouabain-treated 8505C cells. In contrast, decreased mRNA levels of PAX8 and TTF1 differentiation markers and increased levels of the N-cadherin EMT marker, as well as IL-6 and TGFb1, were found in ouabain-treated 8505C cells. In short, ouabain may have anti-proliferative and anti-migratory effect on 8505C cells, but maintains an aggressive and undifferentiated profile.
RESUMEN
Ouabain (OUA) is a glycoside shown to modulate B and T lymphocytes. Nevertheless, ouabain effects on B16F10 melanoma immune response, a mouse lineage that mimics human melanoma, are still unknown. Our aim was to study how OUA in vivo treatment modulates lymphocytes and if it improves the response against B16F10 cells. C57BL/6 mice were pre-treated with intraperitoneal (i.p) injection of OUA (0.56 mg/Kg) for three consecutive days. On the 4th day, 106 B16F10 cells or vehicle were i.p. injected. Animals were euthanized on days 4th and 21st for organs removal and subsequent lymphocyte analyses by flow cytometry. In vivo ouabain-treatment reduced regulatory T cells in the spleen in both melanoma and non-melanoma groups. Ouabain preserved the number and percentage of B lymphocytes in peripheral organs of melanoma-injected mice. Melanoma-injected mice pre-treated with OUA also survive longer. Our findings contribute to a better understanding of OUA immunological effects in a melanoma model.