期刊
BMC COMPLEMENTARY MEDICINE AND THERAPIES
卷 21, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12906-021-03332-z
关键词
Anaplastic thyroid cancer; Artemisinin; Pyrvinium pamoate; Apoptosis; Drug resistance
资金
- Research Fund for Lin He's Academician Workstation of New Medicine and Clinical Translation in Jining Medical University [JYHL2019MS19]
The study demonstrated the efficacy of artemisinin in anaplastic thyroid cancer, and suggested that inhibition of WNT signaling may be the key to overcoming artemisinin resistance.
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 beta-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.
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