Li Yitian
Research Department of Jining Medical University, Jining, Shandong, China.
Anticancer Agents Med Chem. 2022;22(9):1753-1760. doi: 10.2174/1871520621666210910100803.
Anaplastic Thyroid Cancer (ATC) is a rare subtype of thyroid tumors with a high mortality rate. Targeted therapies against ATC are ineffective and mostly transient. Artemisinin has shown excellent anti-tumor activity in several cancers, but its effects on ATC are still unknown.
To evaluate the effects of artemisinin on ATC cells and assess the mechanism underlying drug resistance.
The viability and proliferation rates of the artemisinin-treated CAL-62 and BHT-101 cells were analyzed by MTT and EdU incorporation assays. The protein expression levels were determined by Tandem Mass Tag (TMT) labeling quantitative proteomics and western blotting.
Artemisinin treatment significantly decreased the expression levels of COX2 and COX7A2 and increased that of COX14, YEM1l1, ALAS1, and OAT after 48h. In addition, FTL was upregulated in the CAL-62 cells and downregulated in BHT-101 cells. The CAL-62 cells showed transient and reversible resistance to artemisinin, which was correlated to time-dependent changes in HIF1α, PDK1, and PDHA levels.
Artemisinin targets the mitochondrial respiratory chain proteins in ATC cells. CAL-62 cells show transient resistance to artemisinin via PDH downregulation, indicating that PDH activation may enhance the cytotoxic effects of artemisinin on ATC cells.
间变性甲状腺癌（ATC）是一种罕见的甲状腺肿瘤亚型，死亡率很高。针对ATC的靶向治疗无效，且大多是短暂的。青蒿素在几种癌症中已显示出优异的抗肿瘤活性，但其对ATC的影响仍不清楚。
评估青蒿素对ATC细胞的作用，并评估耐药机制。
通过MTT和EdU掺入试验分析青蒿素处理的CAL-62和BHT-101细胞的活力和增殖率。通过串联质谱标签（TMT）标记定量蛋白质组学和蛋白质印迹法测定蛋白质表达水平。
48小时后，青蒿素处理显著降低了COX2和COX7A2的表达水平，并增加了COX14、YEM1l1、ALAS1和OAT的表达水平。此外，FTL在CAL-62细胞中上调，在BHT-101细胞中下调。CAL-62细胞对青蒿素表现出短暂且可逆的耐药性，这与HIF1α、PDK1和PDHA水平的时间依赖性变化相关。
青蒿素靶向ATC细胞中的线粒体呼吸链蛋白。CAL-62细胞通过PDH下调对青蒿素表现出短暂耐药性，表明PDH激活可能增强青蒿素对ATC细胞的细胞毒性作用。
