title: RNA interference-mediated secretory clusterin gene silencing inhibits proliferation and promotes apoptosis of human non-small cell lung cancer cells.
abstract: OBJECTIVE
  Non-small cell lung cancer (NSCLC) constitutes around 85% of lung cancer cases and is frequently beyond surgical intervention.
  
  
  METHODS
  Secretory clusterin (sCLU) is found in diverse types of human cancers and is unregulated in a variety of cell lines in response to stress, and enhances cancer cell survival. However, the roles of sCLU in NSCLC are still to be elucidated.
  
  
  RESULTS
  Here we show that RNA interference (RNAi)-mediated sCLU gene silencing with short interference RNA (siRNA) strongly decreased the sCLU mRNA and protein levels, as well as suppressed cell proliferation and induced cell apoptosis. In addition, sCLU siRNA also blocked the PI3K/AKT signaling pathway, and decreased the AKT phosphorylation level, but no change was found in total AKT level. More importantly, PI3K/AKT signaling pathway inhibitor, LY294002, also reduced tumor cell proliferation, which is similar to the result with or without sCLU siRNA treatment.
  
  
  CONCLUSIONS
  These results suggest that sCLU plays a positive role in NSCLC cell proliferation, which may be mediated by the PI3K/AKT signaling pathway. Our work in this study demonstrates RNAi-mediated sCLU gene silencing may provide a novel therapeutic strategy in the treatment of NSCLC.
authors.affiliation: Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yan
authors.forename: Kai
authors.initials: K
authors.lastname: Luo
authors.forename: Huiqin
authors.initials: H
authors.lastname: Zhang
authors.forename: Weiran
authors.initials: W
authors.lastname: Chai
mesh_terms: D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051152:Clusterin / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt