Affiliation:
1. Research Department of Jining Medical University Post Address: He Hua Road 133, Jining Medical University, Jining, Shandong, China
Abstract
Background:
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.
Objective:
To evaluate the effects of artemisinin on ATC cells and assess the mechanism underlying drug resistance.
Methods:
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.
Results:
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 HIF1, PDK1, and PDHA levels.
Conclusion:
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.
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
Cited by
1 articles.
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