Esophageal cancer (EC) is a complex gastrointestinal
malignancy and its global incidence rate ranks 7th among all
cancer types. Due to its aggressive nature and the potential for early
metastasis, the survival rates of patients with EC are poor.
Dihydroartemisinin (DHA) is the primary active derivative of
artemisinin, and, as well as its use as an
anti-malarial, DHA has also exhibited antitumor activity in various
cancer models, such as
cholangiocarcinoma, head and neck
carcinoma, and
hepatocellular carcinoma cells. However, the molecular mechanisms underlying the antitumor effect of DHA in the treatment of EC remains poorly understood. The results of the present study demonstrated that DHA significantly inhibited the migration of TE-1 and Eca-109 EC cells in a dose-dependent manner by activating autophagy. DHA treatment also significantly reversed epithelial-mesenchymal transition (EMT) by downregulating the EMT-associated markers,
N-cadherin and
vimentin, and upregulating the expression of
E-cadherin. Mechanistically, DHA treatment decreased Akt phosphorylation and inhibited the Akt/mTOR signaling pathway, leading to the activation of autophagy. The levels of the autophagy-associated
proteins were suppressed and DHA-mediated inhibition of migration in EC cells was reversed when an active form of Akt was overexpressed. In conclusion, the present study demonstrated the potential value of DHA in the treatment of EC, and revealed the underlying mechanism by which FDHA inhibits cellular migration.