Bortezomib induces apoptosis and autophagy in osteosarcoma cells through mitogen-activated protein kinase pathway in vitro.

Objective: To investigate the effects of bortezomib on human osteosarcoma cells from the HOS cell line, and the underlying associated mechanisms.

Methods: Viability of HOS cells treated with bortezomib (5-20 nM) for different time periods was measured and changes in the cell cycle were assessed. Apoptosis and autophagy in HOS cells treated with bortezomib were analysed using annexin V-fluorescein isothiocyanate assay, transmission electron microscopy and Western blotting. Surges in mitogen-activated protein kinase (MAPK) pathways including MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK1/2), ERK1/2, c-Jun N-terminal kinase (JNK) and p38 MAPK were analysed using Western blotting.

Results: Bortezomib induced growth inhibition in a time- and dose-dependent manner, and autophagy and apoptosis in a dose-dependent manner, in HOS cells. HOS cell autophagy and apoptosis in response to bortezomib, corresponded with changing levels of intracellular MAPK signalling molecules.

Conclusions: This study provided new insights into the mechanisms underlying bortezomib-induced apoptosis in human osteosarcoma HOS cells, and suggests that bortezomib could be a potent chemotherapeutic agent in the treatment of osteosarcoma.