Shikonin inhibits the growth of anaplastic thyroid carcinoma cells by promoting ferroptosis and inhibiting glycolysis
Chen Yang,
Lei Yang,
Dihua Li,
Jian Tan,
Qiang Jia,
Huabing Sun,
Zhaowei Meng,
Yan Wang
Affiliations
Chen Yang
Department of Nuclear Medicine, Tianjin Medical University General Hospital, 300052, China; Department of Radiology, Tianjin NanKai Hospital, Tianjin Medical University, 300102, China; Cute Abdominal Disease Related Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Key Laboratory, 300102, China; Institute of Integrative Medicine for Acute Abdominal Diseases, 300102, China
Lei Yang
Department of Radiology, Tianjin NanKai Hospital, Tianjin Medical University, 300102, China; Cute Abdominal Disease Related Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Key Laboratory, 300102, China; Institute of Integrative Medicine for Acute Abdominal Diseases, 300102, China
Dihua Li
Department of Radiology, Tianjin NanKai Hospital, Tianjin Medical University, 300102, China; Cute Abdominal Disease Related Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Key Laboratory, 300102, China; Institute of Integrative Medicine for Acute Abdominal Diseases, 300102, China
Jian Tan
Department of Nuclear Medicine, Tianjin Medical University General Hospital, 300052, China
Qiang Jia
Department of Nuclear Medicine, Tianjin Medical University General Hospital, 300052, China
Huabing Sun
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China
Zhaowei Meng
Department of Nuclear Medicine, Tianjin Medical University General Hospital, 300052, China; Tianjin Key Lab of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, 300052, China; Corresponding author. Department of Nuclear Medicine, Tianjin Medical University General Hospital, 300052, China.
Yan Wang
Chinese Material Medical College, Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617, China; State Key Laboratory of Component- based Chinese Medicine, Jinghai District, 301617, China
Anaplastic thyroid carcinoma is one of the highly fatal cancers and poses a serious threat to human health. Ferroptosis has been widely studied and proved to have an important role in tumor suppression, providing new avenues for cancer therapy; glutathione peroxidase 4(GPX4) and selenoprotein thioredoxin reductase(TXNRD1) are important regulatory targets in ferroptosis.Warburg effect is one of the important energy sources for cancer hypermetabolism, and pyruvate kinase isoenzyme 2 (PKM2) is a key metabolism enzyme that is important in this effect. Shikonin(SKN) is a Chinese herb that has been extensively studied for its anti-tumor ability. The aim of this study was to investigate the mechanism of anti-tumor effect of SKN in ATC cells and to elucidate the role played by ferroptosis and glycolysis in this inhibitory mechanism. The effects of SKN in ATC cell lines CAL-62 and 8505C cells were detected by flow cytometry, Western blotting,real-time quantitative PCR and a fluorescent probe for reactive oxygen species (ROS) to detect changes in intracellular ROS positivity; glucose and lactate assay kits to detect the levels of the raw material of glucose metabolism, glucose (GLU), and the product of glucose metabolism, lactate (LD); and the establishment of the BALB/C nude mice subcutaneous tumor model to analyse the inhibitory effect of SKN on ATC in vivo. The present study demonstrated that SKN inhibits the expression of NF-κB,GPX4,TXNRD1,PKM2,GLUT1.SKN inhibits ATC cell growth by down-regulating the occurrence of intracellular ferroptosis and inhibiting glycolysis in ATC cells.
