Shikonin inhibits the growth of anaplastic thyroid carcinoma cells by promoting ferroptosis and inhibiting glycolysis
10.3760/cma.j.cn311282-20230911-00073
- VernacularTitle:紫草素通过促进铁死亡和抑制糖酵解抑制甲状腺未分化癌细胞生长
- Author:
Chen YANG
1
;
Lei YANG
;
Dihua LI
;
Yan WANG
;
Jian TAN
;
Qiang JIA
;
Zhaowei MENG
Author Information
1. 天津医科大学总医院核医学科，天津 300052
- Keywords:
Shikonin;
Anaplastic thyroid carcinoma;
NF-κB;
Ferroptosis;
Glycolysis
- From:
Chinese Journal of Endocrinology and Metabolism
2024;40(5):420-426
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role and molecular mechanism of Shikonin(SKN) in inhibiting the growth of anaplastic thyroid carcinoma(ATC) cells.Methods:The effect of SKN on ferroptosis in ATC cell lines CAL-62 was detected by flow cytometry; the expression levels of NF-κB, ferroptosis-related genes glutathione peroxidase 4(GPX4) and selenoprotein thioredoxin reductase 1(TXNRD1), glucose metabolism-related genes pyruvate kinase isoform 2(PKM2) and glucose transporter protein 1(GLUT1) were detected by Western blotting; real-time fluorescence quantitative(qPCR) to detect changes in the expression levels of GPX4, PKM2 and GLUT1; reactive oxygen species(ROS) fluorescent probe to detect changes in intracellular ROS positivity; glucose and lactic acid assay kit to detect the levels of glucose, the raw material of glucose metabolism(GLU), and lactate(LD), the product of glucose metabolism; and establishment of a subcutaneous tumour model in BALB/c nude mice to analyse the inhibitory effect of SKN on ATC in vivo.Results:Compared to the control group, after SKN treatment, the protein expression levels of NF-κB, GPX4, TXNRD1, GLUT1, and PKM2 in CAL-62 cells decreased( P=0.004, P=0.012, P=0.043, P=0.001, P=0.018); the mRNA expression of GPX4, GLUT1, and PKM2 also decreased( P<0.001, P=0.029, P<0.001). Additionally, ROS production increased( P=0.041). After treatment with the ferroptosis inhibitor Liproxstatin-1(L-1), the proportion of cell death was reversed to a certain extent, and there was no statistically significant difference in cell death proportion after L-1 treatment. Intracellular ferroptosis occurred( P<0.001), with reduced levels of glutamate(GLU) uptake and lipid peroxidation(LD) generation( P<0.001). SKN inhibited ATC tumor growth in vivo( P=0.016). Conclusion:SKN promotes intracellular ferroptosis in ATC cells, inhibits glycolysis and glucose uptake, and suppresses ATC cell growth.
