Osteosarcoma, the most common primary bone
malignancy, is typically related to growth spurts during adolescence. Prognosis is very poor for patients with metastatic or recurrent
osteosarcoma, with survival rates of only 20-30%. Epithelial-mesenchymal transition (EMT) is a cellular mechanism that contributes to the invasion and
metastasis of
cancer cells, and Wnt signaling activates the EMT program by stabilizing Snail and β-
catenin in tandem. Although the Wnt/Snail axis is known to play significant roles in the progression of
osteosarcoma, and the
anthelmintic agents,
niclosamide and
pyrvinium, have been studied as inhibitors of the Wnt pathway, their
therapeutic effects and regulatory mechanisms in
osteosarcoma remain unidentified. In this study, we show that both
niclosamide and
pyrvinium target Axin2, resulting in the suppression of EMT by the inhibition of the Wnt/Snail axis in
osteosarcoma cells. Axin2 and Snail are abundant in patient samples and cell lines of
osteosarcoma. The treatment of
niclosamide and
pyrvinium inhibits the migration of
osteosarcoma cells at nanomolar concentrations. These results suggest that Axin2 and Snail are candidate therapeutic targets in
osteosarcoma, and that anthelminthic agents,
niclosamide and
pyrvinium, may be effective for
osteosarcoma patients.