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Updated: Nov 4, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Pyrvinium pamoate can overcome artemisinin's resistance in anaplastic thyroid cancer
1Research Department of Jining Medical University, He Hua Road 133, Jining, Shandong, China. liyt@mail.jnmc.edu.cn.
Background:
Anaplastic thyroid carcinoma is a highly lethal subtype of thyroid cancer without effective therapies. Drug resistance in anaplastic thyroid carcinoma poses a significant problem. Although artemisinin exerts antitumor effects, but its efficacy in anaplastic thyroid carcinoma is unknown.
Methods:
We used RNA sequencing to identify differentially expressed genes. Next, we determined the cause of ART resistance by testing the expression and activity of β-catenin, and enhanced ART activity with a WNT signaling inhibitor.
Results:
Artemisinin suppressed the growth of BHT-101 but not human thyroid anaplastic carcinoma (CAL-62) cells. The mechanism of artemisinin resistance in CAL-62 was associated with the aberrant activation of WNT signaling. Pyrvinium pamoate, an inhibitor of WNT signaling, was used to overcome ART resistance in CAL-62 cells. The combination of artemisinin and pyrvinium pamoate suppressed the growth of CAL-62 cells and induced the apoptosis.
Conclusions:
Our study is the first to prove the efficacy of ART as monotherapy or in combination with PP in the management of anaplastic thyroid cancer, and that the inhibition of WNT signaling may overcome ART resistance.
Insights
Artemisinin shows potential against anaplastic thyroid cancer, but resistance can occur. Inhibiting WNT signaling with pyrvinium pamoate may overcome this resistance, offering new therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Anaplastic thyroid carcinoma (ATC) is a deadly cancer with limited treatment options.
- Drug resistance is a major challenge in managing ATC.
- The efficacy of artemisinin (ART) in ATC was previously unknown.
Purpose of the Study:
- To investigate the efficacy of artemisinin in anaplastic thyroid carcinoma.
- To identify mechanisms of artemisinin resistance in ATC.
- To explore strategies for overcoming artemisinin resistance.
Main Methods:
- RNA sequencing was employed to identify differentially expressed genes.
- Beta-catenin expression and activity were assessed to understand ART resistance.
- WNT signaling inhibitors were used to enhance ART activity.
Main Results:
- Artemisinin suppressed BHT-101 cell growth but not CAL-62 cells.
- Aberrant WNT signaling activation was identified as a mechanism of ART resistance in CAL-62 cells.
- The combination of artemisinin and pyrvinium pamoate (PP) inhibited CAL-62 cell growth and induced apoptosis.
Conclusions:
- This study demonstrates the efficacy of artemisinin (ART) as monotherapy or in combination with pyrvinium pamoate (PP) for anaplastic thyroid cancer.
- Inhibition of WNT signaling is a viable strategy to overcome ART resistance in ATC.
- These findings offer potential new therapeutic avenues for managing this lethal cancer.
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