滤泡性甲状腺癌（FTC）是分化型甲状腺癌的一种常见形式，而未分化甲状腺癌（ATC）是一种罕见、快速生长、未分化和高度侵袭性的肿瘤，给根除带来了重大挑战。铁死亡是一种由活性氧的过量产生和随后的脂质过氧化驱动的铁依赖性细胞死亡机制，成为一种有前途的癌症治疗策略。据观察，许多癌细胞表现出对铁死亡的敏感性，而其他一些组织型似乎通过抵消铁超载引起的代谢变化和氧化应激而具有抵抗力。在这里，我们使用人体活检和体外方法来分析铁的影响依赖性细胞死亡。我们通过 MTT 周转、克隆形成分析和细胞荧光辅助分析来评估细胞增殖和活力。使用脂质过氧化测定和蛋白质印迹来分析铁死亡调节的分子机制。使用两种不同的甲状腺癌细胞系：FTC-133（滤泡性）和8505C（间变性）。这些细胞系暴露于铁死亡诱导剂、Erastin 和 RSL3，同时使用柠檬酸铁铵模拟铁过载条件。我们的证据表明，暴露于铁过载的 FTC-133 细胞系会降低其活力并表现出铁死亡增加。相比之下，8505C 细胞系似乎能更好地耐受铁死亡，通过调节 CD71 做出反应，CD71 参与铁内化，似乎在抵抗铁过载方面发挥作用，从而维持细胞活力。研究可能具有临床意义，特别是在解决与 ATC 治疗相关的未满足的治疗需求方面，与 FTC 相比，对铁死亡的抵抗似乎更加明显。© 2023。作者。

Follicular thyroid cancer (FTC) is a prevalent form of differentiated thyroid cancer, whereas anaplastic thyroid cancer (ATC) represents a rare, fast-growing, undifferentiated, and highly aggressive tumor, posing significant challenges for eradication. Ferroptosis, an iron-dependent cell death mechanism driven by the excessive production of reactive oxygen species and subsequent lipid peroxidation, emerges as a promising therapeutic strategy for cancer. It has been observed that many cancer cells exhibit sensitivity to ferroptosis, while some other histotypes appear to be resistant, by counteracting the metabolic changes and oxidative stress induced by iron overload.Here we used human biopsies and in vitro approaches to analyse the effects of iron-dependent cell death. We assessed cell proliferation and viability through MTT turnover, clonogenic assays, and cytofluorimetric-assisted analysis. Lipid peroxidation assay and western blot were used to analyse molecular mechanisms underlying ferroptosis modulation. Two distinct thyroid cancer cell lines, FTC-133 (follicular) and 8505C (anaplastic), were utilized. These cell lines were exposed to ferroptosis inducers, Erastin and RSL3, while simulating an iron overload condition using ferric ammonium citrate.Our evidence suggests that FTC-133 cell line, exposed to iron overload, reduced their viability and showed increased ferroptosis. In contrast, the 8505C cell line seems to better tolerate ferroptosis, responding by modulating CD71, which is involved in iron internalization and seems to have a role in resistance to iron overload and consequently in maintaining cell viability.The differential tolerance to ferroptosis observed in our study may hold clinical implications, particularly in addressing the unmet therapeutic needs associated with ATC treatment, where resistance to ferroptosis appears more pronounced compared to FTC.© 2023. The Author(s).