Dihydroartemisinin inhibits EMT progression in medullary thyroid carcinoma through Hippo signaling pathway regulated by IL-6

Abstract

Abstract Dihydroartemisinin, an artemisinin derivative, has the ability to influence both the inflammatory response and the growth of certain malignancies. In this study, we used the CCK-8 and Transwell assays to show that DHA had a suppressive effect on the growth, migration, and invasion of medullary thyroid cancer cells. Furthermore, we used Elisa, Western blot, and immunofluorescence assays to confirm the expression of transcriptional co-activators YAP/TAZ downstream of the Hippo pathway, as well as changes in the expression of EMT process markers E-cadherin and N-cadherin.The results demonstrated that DHA effectively reduced the expression of IL-6 in medullary thyroid carcinoma cells and hindered their EMT process by regulating the Hippo pathway. This regulation was achieved through the promotion of YAP phosphorylation and the inhibition of YAP/TAZ protein expression.Following additional activation of the Hippo pathway with GA-017, the inhibitory effect of DHA on IL-6 was alleviated. Subsequently, the Hippo pathway was activated, leading to an increase in the expression of E-cadherin, a marker associated with the epithelial-mesenchymal transition (EMT) process. In conclusion, this study demonstrates that DHA can regulate the Hippo pathway by inhibiting IL-6 secretion, leading to the inhibition of the EMT process in medullary thyroid carcinoma. These findings provide a theoretical foundation for further exploring the anticancer mechanism of DHA. Additionally, this study offers valuable insights for the potential clinical application of DHA as a combination drug.