Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological signatures of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma and prostate 6 Gy X-ray resistant cancer cells were characterized by an increase of Lipid Droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 overexpression as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect which might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.

中文翻译：

---

脂滴和铁蛋白重链：人类癌细胞放射抗性中的恶魔联系

尽管在癌症治疗方面取得了很大进展，但癌症放射抗性 (RR) 的分子机制以及放射抗性癌细胞的生物学特征仍有待阐明。在这方面，我们发现乳腺、膀胱、肺、神经胶质瘤和前列腺 6 Gy X 射线抗性癌细胞的特征是脂滴 (LD) 数量增加，并且含有最高 LD 的细胞在照射后表现出最高的克隆形成潜力. 此外，我们观察到 LD 含量与铁代谢密切相关，特别是与铁蛋白重链 (FTH1) 的存在密切相关。事实上，对 FTH1 基因沉默的乳腺癌和肺癌细胞显示出 LD 数量减少，因此变得对放射敏感。FTH1 过表达以及去铁胺的铁螯合处理能够恢复 LD 量和 RR。总体而言，这些结果提供了 RR 背后新机制的证据，其中 LD 和 FTH1 彼此紧密相连，这种协同效应可能值得深入研究，以使癌细胞对放射线更加敏感并提高放射治疗的功效。