title: Autophagy-independent enhancing effects of Beclin 1 on cytotoxicity of ovarian cancer cells mediated by proteasome inhibitors.
abstract: BACKGROUND
  The ubiquitin-proteasome system and macroautophagy (hereafter referred to autophagy) are two complementary pathways for protein degradation. Emerging evidence suggests that proteasome inhibition might be a promising approach for tumor therapy. Accumulating data suggest that autophagy is activated as a compensatory mechanism upon proteasome activity is impaired.
  
  
  METHODS
  Autophagy activation was measured using acridine orange staining and LC3 transition. Cell viability and apoptosis were measured using MTT assay and flow cytometry, respectively. Beclin 1 expression vectors or shRNA against Beclin 1 (shBeclin 1) were transfected to investigate the role of Beclin 1 in autophagy activation and cytotoxicity of ovarian cancer cells induced by proteasome inhibitors.
  
  
  RESULTS
  Proteasome inhibitors suppressed proliferation and induced autophagy in ovarian cancer cells. Neither phosphoinositide 3-kinase (PI3K) inhibitors nor shRNA against Beclin 1 could abolish the formation of acidic vacuoles and the processing of LC3 induced by proteasome inhibitors. Moreover, Beclin 1 overexpression enhanced anti-proliferative effects of proteasome inhibitors in ovarian cancer cells.
  
  
  CONCLUSIONS
  For the first time, the current study demonstrated that proteasome inhibitors induced PI3K and Beclin 1-independent autophagy in ovarian cancer cells. In addition, this study revealed autophagy-independent tumor suppressive effects of Beclin 1 in ovarian cancer cells.
authors.affiliation: Department of Obstetrics & Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Yan
authors.forename: Hua-Qin
authors.initials: HQ
authors.lastname: Wang
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Gao
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Liu
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Hu
authors.forename: Dawo
authors.initials: D
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.forename: Bei
authors.initials: B
authors.lastname: Lin
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D000071186:Beclin-1; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D061988:Proteasome Inhibitors; D047428:Protein Kinase Inhibitors