Osteosarcoma is the most common primary bone cancer, primarily affecting children and young adults. Cancer stem cells (CSCs), a subpopulation presenting stemness, critically influence prognosis and promote recurrence and metastasis. Due to the crucial role of glycogen synthase kinase‑3 beta (GSK‑3β) in maintaining stemness, it is considered as an important target for drug development. The aim of the present study was to evaluate the inhibitory effect of AZD1080, a GSK‑3β inhibitor, on osteosarcoma CSCs. AZD1080 treatment clearly inhibited sphere formation in U2OS and 143B cells and dissociated spheres in CSCs derived from U2OS and 143B; in both processes, stemness markers OCT4 and SOX2 were markedly decreased, without affecting cell proliferation or apoptosis. AZD1080 treatment inhibited phosphorylation of GSK‑3β and its downstream regulated genes, including HEY1, HES1, CyclinD1 and β‑catenin. It was also observed that GSK‑3β activity was critical for the inhibitory effects of AZD1080 treatment on sphere formation and stemness. Moreover, GSK‑3β knockdown inhibited sphere formation and invasion capacity, indicating that AZD1080 exerts inhibitory roles in a GSK‑3β‑dependent manner. Taken together, the results showed AZD1080 as a specific inhibitor of CSC stemness, without cytotoxicity, and indicated it was a promising therapeutic agent that targeted GSK‑3β signaling in osteosarcoma.
Keywords: AZD1080; cancer stem‑like cells; epithelial‑mesenchymal transition; glycogen synthase kinase‑3β; osteosarcoma.