Papillary thyroid cancer can dedifferentiate into a much more aggressive form of thyroid cancer, namely into anaplastic thyroid cancer. Nrf2 is commonly activated in papillary thyroid cancer, whereas its role in anaplastic thyroid cancer has not been fully explored. In this study, we used two cell lines and an animal model to examine the function of Nrf2 in anaplastic thyroid cancer. The role of Nrf2 in anaplastic thyroid cancer was investigated by a series of functional studies in two anaplastic thyroid cancer cell lines, FRO and KAT-18, and further confirmed with an in vivo study. The impact of Nrf2 on the sensitivity of anaplastic thyroid cancer cells to lenvatinib was also investigated to evaluate its potential clinical implication. We found that the expression of Nrf2 was significantly higher in anaplastic thyroid cancer cell line cells than in papillary thyroid cancer cells or normal control cells. Knockdown of Nrf2 in anaplastic thyroid cancer cells inhibited their viability and clonogenicity, reduced their migration and invasion ability in vitro, and suppressed their tumorigenicity in vivo. Mechanistically, knockdown of Nrf2 decreased the expression of Notch1. Lastly, knockdown of Nrf2 increased the sensitivity of anaplastic thyroid cancer cells to lenvatinib. As knockdown of Nrf2 reduced the metastatic and invasive ability of anaplastic thyroid cancer cells by inhibiting the Notch 1 signaling pathway and increased the cancer cell sensitivity to lenvatinib, Nrf2 could be a promising therapeutic target for patients with anaplastic thyroid cancer.

中文翻译：

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Nrf2 的敲低抑制了肿瘤生长并增加了间变性甲状腺癌对 Lenvatinib 的敏感性

乳头状甲状腺癌可以分化为更具侵袭性的甲状腺癌，即未分化甲状腺癌。Nrf2 通常在甲状腺乳头状癌中被激活，而其在未分化甲状腺癌中的作用尚未得到充分探索。在这项研究中，我们使用两个细胞系和一个动物模型来检查 Nrf2 在未分化甲状腺癌中的功能。Nrf2 在未分化甲状腺癌中的作用通过对两种未分化甲状腺癌细胞系 FRO 和 KAT-18 的一系列功能研究进行了研究，并通过体内实验进一步证实学习。还研究了 Nrf2 对间变性甲状腺癌细胞对乐伐替尼敏感性的影响，以评估其潜在的临床意义。我们发现 Nrf2 的表达在未分化甲状腺癌细胞系细胞中显着高于乳头状甲状腺癌细胞或正常对照细胞。甲状腺未分化癌细胞中 Nrf2 的敲低抑制了它们的活力和克隆形成，降低了它们在体外的迁移和侵袭能力，并抑制了它们在体内的致瘤性. 从机制上讲，Nrf2 的敲低降低了 Notch1 的表达。最后，Nrf2 的敲低增加了间变性甲状腺癌细胞对乐伐替尼的敏感性。由于 Nrf2 的敲低通过抑制 Notch 1 信号通路降低了未分化甲状腺癌细胞的转移和侵袭能力，并增加了癌细胞对乐伐替尼的敏感性，因此 Nrf2 可能成为未分化甲状腺癌患者的一个有前途的治疗靶点。