Ouabain is a steroid described as a compound extracted from plants that is capable of binding to Na⁺, K⁺-ATPase, inhibiting ion transport and triggering cell signaling pathways. Due to its positive ionotropic effect, ouabain was used for more than 200 years for the treatment of cardiac dysfunctions. Numerous antitumor effects of ouabain have been described so far; however, its role on thyroid cancer is still poorly understood. Therefore, the aim of the present work was to evaluate the effect of ouabain on the biology of human papillary thyroid cancer cells. For this, three human thyroid cell lines were used: NTHY-ori, a non-tumor lineage, BCPAP and TPC-1, both derived from papillary carcinomas. Cells were cultured in the presence or absence of ouabain. Subsequently, we evaluated its effects on the viability, cell death, cell cycle, and migratory ability of these cell lines. We also investigated the impact of ouabain in IL-6/IL-6R and epithelial to mesenchymal transition markers expression. Our results indicate that ouabain (10⁻⁷ M), decreased the number of NTHY-ori, TPC-1 and BCPAP viable cells and induced cell cycle arrest after in vitro culture, but did not appear to promote cell death. In TPC-1 cells ouabain also inhibited cell migration; increased IL-6/IL-6R expression and IL-6 secretion; and diminished vimentin and SNAIL-1 expression. Collectively, our results indicate that ouabain has an antitumoral role on human papillary thyroid carcinomas in vitro. Even though additional studies are necessary, our work contributes to the discussion of the possibility of new clinical trials of ouabain.

中文翻译：

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类固醇哇巴因对人甲状腺乳头状癌细胞系的体外抗肿瘤作用

哇巴因是一种类固醇，被描述为从植物中提取的能够与 Na ⁺、 K ^{+结合的化合物}-ATPase，抑制离子转运和触发细胞信号通路。由于其正离子作用，哇巴因用于治疗心脏功能障碍已有 200 多年的历史。迄今为止，已经描述了哇巴因的多种抗肿瘤作用；然而，它在甲状腺癌中的作用仍然知之甚少。因此，本工作的目的是评估哇巴因对人乳头状甲状腺癌细胞生物学的影响。为此，使用了三种人类甲状腺细胞系：NTHY-ori，一种非肿瘤谱系，BCPAP 和 TPC-1，均来源于乳头状癌。在存在或不存在哇巴因的情况下培养细胞。随后，我们评估了它对这些细胞系的活力、细胞死亡、细胞周期和迁移能力的影响。我们还研究了哇巴因对 IL-6/IL-6R 和上皮间质转化标志物表达的影响。我们的结果表明哇巴因 (10^-7 M)，减少 NTHY-ori、TPC-1 和 BCPAP 活细胞的数量并在体外培养后诱导细胞周期停滞，但似乎没有促进细胞死亡。在 TPC-1 细胞中，哇巴因还抑制细胞迁移。增加 IL-6/IL-6R 表达和 IL-6 分泌；并减少波形蛋白和 SNAIL-1 的表达。总的来说，我们的结果表明哇巴因在体外对人乳头状甲状腺癌具有抗肿瘤作用。尽管需要进行额外的研究，但我们的工作有助于讨论哇巴因新临床试验的可能性。