Dihydroartemisinin inhibits tumor growth of human osteosarcoma cells by suppressing Wnt/β-catenin signaling

Abstract

Osteosarcoma (OS) is the most common type of bone cancer. Even with early diagnosis and aggressive treatment, the prognosis for OS is poor. In the present study, we investigated the proliferation and invasion inhibitory effect of dihydroartemisinin (DHA) on human OS cells and the possible molecular mechanisms involved. We demonstrated that DHA can inhibit proliferation, decrease migration, reduce invasion and induce apoptosis in human OS cells. Using an in vivo tumor animal model, we confirmed that DHA can prevent OS formation and maintain intact bone structure in athymic mice. In addition, we examined the possible molecular mechanisms mediating the function of DHA. We found that the total protein levels and transcriptional activity of β-catenin in OS cells are reduced by DHA treatment, and this may result from the increased catalytic activity of glycogen synthase kinase 3β (GSK3β). Moreover, the inhibitory effect of DHA on OS cells is reversed by overexpression of β-catenin, but is further enhanced by knockdown of β-catenin, respectively. Collectively, our results reveal that DHA can inhibit tumor growth of OS cells by inactivating Wnt/β-catenin signaling. Therefore, DHA is a promising chemotherapy agent in the treatment of human OS.