Research Department of Jining Medical University, He Hua Road 133, Jining, Shandong, China.
BMC Complement Med Ther. 2021 May 28;21(1):156. doi: 10.1186/s12906-021-03332-z.
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.
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.
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.
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.
间变性甲状腺癌是一种具有高度致命性的甲状腺癌亚型，目前尚无有效的治疗方法。间变性甲状腺癌的耐药性是一个重大问题。青蒿素虽然具有抗肿瘤作用，但在间变性甲状腺癌中的疗效尚不清楚。
我们使用 RNA 测序来鉴定差异表达的基因。接下来，我们通过测试 β-连环蛋白的表达和活性来确定 ART 耐药的原因，并使用 WNT 信号抑制剂增强 ART 活性。
青蒿素抑制 BHT-101 但不抑制人甲状腺间变性癌（CAL-62）细胞的生长。CAL-62 中青蒿素耐药的机制与 WNT 信号的异常激活有关。WNT 信号抑制剂吡喹酮可克服 CAL-62 细胞对 ART 的耐药性。青蒿素和吡喹酮联合抑制 CAL-62 细胞的生长并诱导细胞凋亡。
我们的研究首次证明了 ART 单药或与 PP 联合治疗间变性甲状腺癌的疗效，抑制 WNT 信号可能克服 ART 耐药性。
