金诺芬抑制葡萄糖摄取并诱导未分化甲状腺癌铁死亡

doi:10.11958/20251716

天津医药 ›› 2026, Vol. 54 ›› Issue (6): 570-576.doi: 10.11958/20251716

金诺芬抑制葡萄糖摄取并诱导未分化甲状腺癌铁死亡

邓新宜¹(), 杨晨¹^,², 曹建林¹^,³, 杨磊⁴, 谭建¹, 贾强¹, 孟召伟¹^,⁵^,^△()

¹ 天津医科大学总医院核医学科（邮编300052）
² 天津市南开医院放射科
³ 山西省人民医院妇产科超声室
⁴ 天津市南开医院急性腹部疾病相关器官损伤与ITCWM修复实验室
⁵ 天津市功能影像重点实验室和天津市影像医学研究所，天津医科大学总医院

收稿日期:2025-08-07 修回日期:2025-12-20 出版日期:2026-06-15 发布日期:2026-06-15
通讯作者: ^△E-mail：zmeng@tmu.edu.cn
作者简介:邓新宜（2002），女，硕士在读，主要从事核医学与甲状腺疾病方面研究。E-mail：15717532014@163.com
基金资助:
国家自然科学基金资助项目(81971650);天津市医学重点学科（专科）建设项目(TJYXZDXK-001A);天津市科委基金(21JCYBJC01820);天津市医学重点学科建设项目(TJYXZDXK-3-003B)

Auranofin inhibits glucose uptake and induces ferroptosis in anaplastic thyroid cancer

DENG Xinyi¹(), YANG Chen¹^,², CAO Jianlin¹^,³, YANG Lei⁴, TAN Jian¹, JIA Qiang¹, MENG Zhaowei¹^,⁵^,^△()

¹ Department of Nuclear Medicine, Tianjin Medical University General Hospital， Tianjin 300052, China
² Department of Radiology, Nankai Hospital
³ Department of Obstetrics and Gynaecology, Shanxi Provincial People's Hospital
⁴ Tianjin Nankai Hospital Laboratory for Organ Injury and ITCWM Repair Related to Acute Abdominal Diseases
⁵ Tianjin Key Laboratory of Functional Imaging and Tianjin Institute of Imaging Medicine, Tianjin Medical University General Hospital

Received:2025-08-07 Revised:2025-12-20 Published:2026-06-15 Online:2026-06-15
Contact: ^△E-mail：zmeng@tmu.edu.cn

邓新宜, 杨晨, 曹建林, 杨磊, 谭建, 贾强, 孟召伟. 金诺芬抑制葡萄糖摄取并诱导未分化甲状腺癌铁死亡[J]. 天津医药, 2026, 54(6): 570-576.

DENG Xinyi, YANG Chen, CAO Jianlin, YANG Lei, TAN Jian, JIA Qiang, MENG Zhaowei. Auranofin inhibits glucose uptake and induces ferroptosis in anaplastic thyroid cancer[J]. Tianjin Medical Journal, 2026, 54(6): 570-576.

摘要/Abstract

摘要：

目的探讨金诺芬（AUF）抑制葡萄糖摄取并诱导未分化甲状腺癌（ATC）细胞铁死亡的作用及其分子机制。方法常规培养CAL-62细胞，以不同浓度（0、0.2、0.4、0.6、0.8、1.0、1.2 μmol/L）AUF处理细胞；并使用0.6 μmol/L AUF单药（AUF组）、BAY单药（BAY组）、0.6 μmol/L AUF+BAY联用（AUF+BAY组）、Eratsin单药（Eratsin组）及0.6 μmol/L AUF+Eratsin联用（AUF+Eratsin组）处理细胞，另设未经药物处理的细胞为对照组。采用CCK-8法检测CAL-62细胞活力，流式细胞术检测细胞凋亡情况。使用葡萄糖检测试剂盒测定细胞葡萄糖摄取水平，铁死亡相关试剂盒检测细胞内铁含量，谷胱甘肽（GSH）提取试剂盒检测GSH含量。采用实时荧光定量聚合酶链反应（qRT-PCR）检测ATC组织中葡萄糖转运体1（GLUT1）mRNA、长链酰基辅酶A合成酶4（ACSL4）mRNA、谷胱甘肽过氧化物酶4（GPX4）mRNA的表达。建立裸鼠皮下移植瘤模型，评估AUF对ATC的体内抑瘤效果；Western blot检测ACSL4、GPX4及硫氧还蛋白还原酶1（TXNRD1）蛋白的表达。结果与对照组相比，AUF对CAL-62细胞活力的抑制呈剂量依赖性(P<0.01)，AUF单药及其与BAY或Erastin的联合处理均能增加细胞凋亡率（P<0.05）；与对照组相比，0.8、1.0 μmol/L AUF组细胞培养基上清液中葡萄糖残余量、细胞内铁含量均升高，GSH含量均降低（P<0.05）。与对照组相比，0.6、0.8、1.0 μmol/L AUF组细胞中GLUT1 mRNA、GPX4 mRNA的表达水平降低（P<0.05），0.8、1.0 μmol/L AUF组细胞中ACSL4 mRNA的表达水平升高（P<0.05）。在动物实验中，仅在第14天观察到AUF+Erastin组肿瘤体积较对照组减小（P<0.05），AUF组肿瘤体积与对照组差异无统计学意义（P>0.05）；各组小鼠体质量与对照组差异均无统计学意义（P>0.05）。与对照组相比，AUF组TXNRD1、GPX4蛋白表达水平降低，ACSL4蛋白表达水平升高（P<0.05），AUF+Erastin组GPX4蛋白表达水平降低，ACSL4蛋白表达水平升高（P<0.05）。结论 AUF能够促进ATC细胞铁死亡并抑制其葡萄糖摄取，从而抑制ATC细胞生长。

关键词: 金诺芬, 甲状腺癌, 未分化, 铁死亡, 葡萄糖摄取, TXNRD1, GLUT1

Abstract:

Objective To investigate the effect and molecular mechanism of auranofin (AUF) in inhibiting glucose uptake and inducing ferroptosis in anaplastic thyroid carcinoma (ATC) cells. Methods CAL-62 cells were routinely cultured and treated with AUF at various concentrations (0, 0.2, 0.4, 0.6, 0.8, 1.0 and 1.2 μmol/L). Cells were also treated with 0.6 μmol/L AUF (AUF group), BAY (BAY group), the combination of 0.6 μmol/L AUF and BAY (AUF+BAY group), Erastin (Erastin group) and the combination of 0.6 μmol/L AUF and Erastin (AUF+Erastin group). Untreated cells were served as the control group. Cell viability of CAL-62 cells was detected by CCK-8 assay, and cell apoptosis was determined by flow cytometry. Glucose uptake was measured using a glucose detection kit, and intracellular iron content and glutathione (GSH) levels were determined using ferroptosis-related assay kits. The mRNA expressions of glucose transporter 1 (GLUT1), long-chain acyl-CoA synthetase 4 (ACSL4) and glutathione peroxidase 4 (GPX4) in ATC tissue were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A subcutaneous xenograft tumor model was established in nude mice to evaluate the antitumor effect of AUF on ATC in vivo. The protein expression levels of ACSL4, GPX4 and thioredoxin reductase 1 (TXNRD1) were detected by Western blot assay. Results Compared with the control group, AUF inhibited the viability of CAL-62 cells in a dose-dependent manner (P<0.01). Both AUF alone and its combined treatment with BAY or Erastin increased the apoptosis rate (P<0.05). Compared with the control group, the residual glucose content in the cell culture supernatant and intracellular iron content were increased, while the GSH content was decreased in the 0.8 and 1.0 μmol/L AUF groups (P<0.05). Compared with the control group, the mRNA expression levels of GLUT1 and GPX4 were decreased in the 0.6, 0.8 and 1.0 μmol/L AUF groups (P<0.05), and the mRNA expression level of ACSL4 was increased in the 0.8 and 1.0 μmol/L AUF groups (P<0.05). In animal experiments, the tumor volume was significantly smaller in the AUF+Erastin group than that in the control group only on day 14 (P<0.05), while there was no statistically significant difference in tumor volume between the AUF group and the control group (P>0.05). There was no statistically significant difference in body weight between each group and the control group (P>0.05). Compared with the control group, the protein expression levels of TXNRD1 and GPX4 were decreased and the protein expression level of ACSL4 was increased in the AUF group (P<0.05). The protein expression level of GPX4 was decreased and the protein expression level of ACSL4 was increased in the AUF+Erastin group (P<0.05). Conclusion AUF promotes ferroptosis and suppresses glucose uptake in ATC cells, thereby inhibiting their proliferation.

Key words: auranofin, thyroid carcinoma, anaplastic, ferroptosis, glucose uptake, TXNRD1, GLUT1

中图分类号:

R736

图/表 12

参考文献 22

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基因名称	引物序列（5'→3'）	产物大小/bp
GLUT1	上游：GGCCAAGAGTGTGCTAAAGAA 下游：ACAGCGTTGATGCCAGACAG	201
ACSL4	上游：CATCCCTGGAGCAGATACTCT 下游：TCACTTAGGATTTCCCTGGTCC	96
GPX4	上游：GAGGCAAGACCGAAGTAAACTAC 下游：CCGAACTGGTTACACGGGAA	100
GAPDH	上游：GGAGCGAGATCCCTCCAAAAT 下游：GGCTGTTGTCATACTTCTCATGG	197

基因名称	引物序列（5'→3'）	产物大小/bp
GLUT1	上游：GGCCAAGAGTGTGCTAAAGAA 下游：ACAGCGTTGATGCCAGACAG	201
ACSL4	上游：CATCCCTGGAGCAGATACTCT 下游：TCACTTAGGATTTCCCTGGTCC	96
GPX4	上游：GAGGCAAGACCGAAGTAAACTAC 下游：CCGAACTGGTTACACGGGAA	100
GAPDH	上游：GGAGCGAGATCCCTCCAAAAT 下游：GGCTGTTGTCATACTTCTCATGG	197

组别	葡萄糖浓度/（n=4，mmol/L）	铁含量/（n=3，ng/10⁴ cell）	GSH含量/（n=4，μg/10⁶prot）
对照组	8.60±1.64	3.92±0.49	1.32±0.02
0.6 μmol/L AUF组	13.23±2.58	6.86±1.77	0.89±0.01^a
0.8 μmol/L AUF组	23.44±3.71^ab	8.16±1.41^a	0.99±0.21^a
1.0 μmol/L AUF组	34.83±3.28^abc	11.59±2.26^ab	0.68±0.01^ac
F	64.160^＊＊	11.590^＊＊	24.810^＊＊

组别	葡萄糖浓度/（n=4，mmol/L）	铁含量/（n=3，ng/10⁴ cell）	GSH含量/（n=4，μg/10⁶prot）
对照组	8.60±1.64	3.92±0.49	1.32±0.02
0.6 μmol/L AUF组	13.23±2.58	6.86±1.77	0.89±0.01^a
0.8 μmol/L AUF组	23.44±3.71^ab	8.16±1.41^a	0.99±0.21^a
1.0 μmol/L AUF组	34.83±3.28^abc	11.59±2.26^ab	0.68±0.01^ac
F	64.160^＊＊	11.590^＊＊	24.810^＊＊

组别	GLUT1	GPX4	ACSL4
对照组	1.00±0.00	1.00±0.00	1.00±0.00
0.6 μmol/L AUF组	0.59±0.19^a	0.75±0.08^a	1.14±0.07
0.8 μmol/L AUF组	0.44±0.05^a	0.40±0.06^ab	1.48±0.05^ab
1.0 μmol/L AUF组	0.62±0.10^a	0.79±0.05^ac	1.71±0.17^ab
F	13.590^＊＊	56.640^＊＊	33.950^＊＊

金诺芬抑制葡萄糖摄取并诱导未分化甲状腺癌铁死亡

Auranofin inhibits glucose uptake and induces ferroptosis in anaplastic thyroid cancer

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参考文献 22

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组别		2 d		4 d		6 d
对照组		337.6±63.9		412.9±162.2		461.9±184.5
AUF组		343.5±123.5		341.5±105.1		334.9±144.4
AUF+Erastin组		298.6±167.6		271.7±151.5		279.5±166.7
F		0.113		0.744		0.952
组别	8 d		10 d		12 d		14 d
对照组	552.8±143.8		608.9±228.9		649.8±269.3		721.2±235.7
AUF组	361.1±118.9		369.6±167.3		378.8±152.0		411.4±138.5
AUF+Erastin组	252.4±143.3		298.2±180.4		253.8±155.3		274.8±171.4^a
F	3.762		2.110		3.080		4.522

组别		2 d		4 d		6 d
对照组		19.00±0.87		19.00±0.53		18.90±0.46
AUF组		17.73±0.64		18.23±0.91		17.93±0.98
AUF+Erastin组		19.47±3.23		20.13±2.58		19.90±2.17
F		0.606		1.062		1.489
组别	8 d		10 d		12 d		14 d
对照组	19.17±0.81		19.40±0.69		18.80±0.26		19.53±0.40
AUF组	17.53±0.72		16.97±0.81		17.93±0.25		18.10±0.72
AUF+Erastin组	20.33±1.82		20.37±2.21		20.40±2.11		20.30±2.17
F	3.983		4.606		3.055		2.089

组别	TXNRD1	GPX4	ACSL4
对照组	0.99±0.13	1.12±0.26	0.28±0.22
AUF组	0.49±0.06	0.62±0.08^a	0.96±0.12^a
AUF+Erastin组	-	0.36±0.08^a	0.73±0.22^a
t或F	5.938^＊＊	16.810^＊＊	9.727^＊

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