title: Bortezomib induces apoptosis and autophagy in osteosarcoma cells through mitogen-activated protein kinase pathway in vitro.
abstract: 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.
authors: Musculoskeletal Tumour Centre, People's Hospital, Peking University, Beijing, China.
authors: Zhiyuan
authors: Z
authors: Lou
authors: Tingting
authors: T
authors: Ren
authors: Xianbo
authors: X
authors: Peng
authors: Yifeng
authors: Y
authors: Sun
authors: Guangjun
authors: G
authors: Jiao
authors: Qunshan
authors: Q
authors: Lu
authors: Shuai
authors: S
authors: Zhang
authors: Xinchang
authors: X
authors: Lu
authors: Wei
authors: W
authors: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010011:Osteocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; autophagy; bortezomib; cell-cycle arrest; mitogen-activated protein kinase (MAPK); osteosarcoma; proteasome inhibition; transmission electron microscopy (TEM)