Autophagic blockade potentiates anlotinib-mediated ferroptosis in anaplastic thyroid cancer.

IF 4.1 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine-related cancer Pub Date : 2023-08-01 Print Date: 2023-09-01 DOI:10.1530/ERC-23-0036

Jiajun Wu, Juyong Liang, Ruiqi Liu, Tian Lv, Kangyin Fu, Liehao Jiang, Wenli Ma, Yan Pan, Zhuo Tan, Qing Liu, Weihua Qiu, Minghua Ge, Jiafeng Wang

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引用次数: 0

Abstract

Anlotinib-mediated angiogenic remodeling was delineated in various tumors. Meanwhile, we previously showed that anlotinib inhibited tumor angiogenesis in anaplastic thyroid cancer (ATC). However, the potential role of anlotinib on cell lethality in ATC remains an enigma. Herein, we found that anlotinib inhibited the viability, proliferation, and migration of KHM-5M, C643, and 8505C cells in a dose-dependently manner. Under anlotinib treatment, PANoptosis (pyroptosis, apoptosis, and necroptosis) markers were not changed; however, ferroptosis targets (transferrin, HO-1, FTH1, FTL, and GPX4) were significantly downregulated. ROS levels also increased in a concentration-dependent manner after anlotinib treatment in KHM-5M, C643, and 8505C cells. In addition, protective autophagy was activated in response to anlotinib, and autophagic blockade potentiated anlotinib-mediated ferroptosis and antitumor effects in vitro and in vivo. Our new discovery identified autophagy-ferroptosis signaling pathway which provides mechanistic insight into anlotinib-mediated cell death, and synergistic combination therapy may help develop new ATC treatment strategies.

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自噬阻断增强了间变性甲状腺癌症中安洛替尼介导的脱铁性贫血。

安洛替尼介导的血管生成重塑在各种肿瘤中被描述。同时，我们先前发现安洛替尼抑制间变性甲状腺癌症（ATC）中的肿瘤血管生成。然而，安洛替尼对ATC细胞致死性的潜在作用仍然是个谜。在此，我们发现安洛替尼以剂量依赖性的方式抑制KHM-5M、C643和8505C细胞的活力、增殖和迁移。在安洛替尼治疗下，PANoptosis（焦下垂、细胞凋亡和坏死）标志物没有改变；然而，脱铁靶点（转铁蛋白、HO-1、FTH1、FTL和GPX4）显著下调。安洛替尼处理KHM-5M、C643和8505C细胞后，ROS水平也以浓度依赖性方式增加。此外，对安洛替尼的反应激活了保护性自噬，自噬阻断增强了安洛替尼介导的脱铁作用和体内外抗肿瘤作用。我们的新发现确定了自噬脱铁信号通路，该通路为安洛替尼介导的细胞死亡提供了机制见解，协同联合治疗可能有助于开发新的ATC治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine-related cancer 医学-内分泌学与代谢

CiteScore

7.80

自引率

2.60%

发文量

138

审稿时长

6-12 weeks

期刊介绍： Endocrine-Related Cancer is an official flagship journal of the Society for Endocrinology and is endorsed by the European Society of Endocrinology, the United Kingdom and Ireland Neuroendocrine Society, and the Japanese Hormones and Cancer Society. Endocrine-Related Cancer provides a unique international forum for the publication of high quality original articles describing novel, cutting edge basic laboratory, translational and clinical investigations of human health and disease focusing on endocrine neoplasias and hormone-dependent cancers; and for the publication of authoritative review articles in these topics. Endocrine neoplasias include adrenal cortex, breast, multiple endocrine neoplasia, neuroendocrine tumours, ovary, prostate, paraganglioma, parathyroid, pheochromocytoma pituitary, testes, thyroid and hormone-dependent cancers. Neoplasias affecting metabolism and energy production such as bladder, bone, kidney, lung, and head and neck, are also considered.