Abstract
BackgroundAnaplastic 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.MethodsWe 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.ResultsArtemisinin 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.ConclusionsOur 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.
Highlights
Anaplastic thyroid carcinoma is a highly lethal subtype of thyroid cancer without effective therapies
ART suppresses the growth of BHT-101 and resistance in CAL-62 cells Results of the CCK-8 proliferation assay (Fig. 1A) revealed that the OD values of BHT-101 cells decreased significantly in a dose-dependent manner (p < 0.05) after treatment with 100, 150, and 200 μM ART for 48 h compared with the control group treated with 0.2% DMSO
No significant differences (p > 0.05) were observed in the OD values (Fig. 1A) of CAL-62 compared with the control cells treated with 0.2% DMSO, or compared with cells treated with ART for 24 h and 48 h
Summary
Anaplastic thyroid carcinoma is a highly lethal subtype of thyroid cancer without effective therapies. Drug resistance in anaplastic thyroid carcinoma poses a significant problem. Artemisinin exerts antitumor effects, but its efficacy in anaplastic thyroid carcinoma is unknown. According to the Global Cancer Statistics 2020, TC has been ranked as the fifth most common malignant tumor in women [1]. Anaplastic thyroid cancer (ATC) is a subtype of TC that accounts for only 2–3% of TC [2]; it is one of the most aggressive forms of TC. ATC is considered invasive or metastatic at diagnosis, regardless of the tumor size, lymph node metastases, or distant metastases, and is classified as stage IV TC by the American Joint Committee on Cancer [4].
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