Background: Doxorubicin (Dox) resistance is a primary obstacle for the treatment of osteosarcoma. Meanwhile, β-Elemene was shown to exhibit an anti-proliferative effect on osteosarcoma cells. However, the role of a combination of Dox with β-Elemene on osteosarcoma cells remains unclear. Thus, this study aimed to investigate the role of the combination of Dox with β-Elemene on the proliferation, apoptosis and oxidative stress of Dox-resistance osteosarcoma cells.
Methods: CKC-8, EdU staining and flow cytometry assays were used to determine the viability, proliferation and apoptosis of Dox-resistance osteosarcoma cells, respectively. Meanwhile, the expression of antioxidant protein peroxiredoxin-1 (Prx-1) in Dox-resistance osteosarcoma cells was detected with Western blot assay.
Results: In this study, the inhibitory effects of Dox on the viability and proliferation of Dox-resistance osteosarcoma cells were significantly enhanced by β-Elemene. In addition, the combination of Dox and β-Elemene markedly induced the apoptosis and oxidative stress in Dox-resistance osteosarcoma cells. Moreover, combination treatment notably downregulated the expression of Prx-1 in Dox-resistance osteosarcoma cells, indicating that combination treatment inhibited the antioxidant capacity of Dox-resistance osteosarcoma cells. In vivo experiments confirmed that β-Elemene could enhance the anti-tumor effect of Dox in Saos-2/Dox xenograft model.
Conclusion: We found that β-Elemene could reverse Dox resistance in Dox-resistance osteosarcoma cells via inhibition of Prx-1. Therefore, combining Dox with β-Elemene might be considered as a therapeutic approach for the treatment of Dox-resistant osteosarcoma.
Keywords: osteosarcoma, doxorubicin, β-Elemene, resistance, apoptosis