title: Inhibition of autophagy enhances the cytotoxic effect of PA-MSHA in breast cancer.
abstract: BACKGROUND
  PA-MSHA, a genetically engineered Pseudomonas aeruginosa (PA) strain, is currently under investigation as a new anti-cancer drug. It can induce cell cycle arrest and apoptosis in different human cancer cells, including hormone receptor negative breast cancer cells. However, the underlying mechanism of tumor lethality mediated by PA-MSHA remains to be fully investigated.
  
  
  METHODS
  The effect of PA-MSHA on human hormone receptor negative breast cancer cells was analyzed by morphological measurement, western blot, cell proliferation assay and mouse xenograft model.
  
  
  RESULTS
  PA-MSHA was found to induce endoplasmic reticulum (ER) stress in breast cancer cell lines through the IRE1 signaling pathway. Inhibiting autophagy potentiated the cytotoxic effect of PA-MSHA while treating breast cancer cell lines. In mouse xenograft model, PA-MSHA produced more pronounced tumor suppression in mice inoculated with IRE1 gene knockdown. MDA-MB-231HM cells.
  
  
  CONCLUSIONS
  These findings demonstrated inhibiting autophagy together with PA-MSHA might be a promising therapeutic strategy in treating hormone receptor negative breast cancer cells.
authors.forename: Wen-Huan
authors.initials: WH
authors.lastname: Xu
authors.forename: Zhe-Bin
authors.initials: ZB
authors.lastname: Liu
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Hou
authors.forename: Qi
authors.initials: Q
authors.lastname: Hong
authors.forename: Da-Li
authors.initials: DL
authors.lastname: Hu
authors.affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P,R, China. zhimingshao@yahoo.com.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004722:Endoribonucleases / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D006388:Hemagglutinins / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D006388:Hemagglutinins; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
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