title: BAD overexpression inhibits cell growth and induces apoptosis via mitochondrial-dependent pathway in non-small cell lung cancer.
abstract: BACKGROUND
  The pro-apoptotic Bcl-2 protein BAD initiated apoptosis in human cells and has been identified as a prognostic marker in non-small cell lung cancer (NSCLC). In this study, we aimed to explore the functions of BAD in NSCLC.
  
  
  METHODS
  Overexpression of BAD was performed by transfecting different NSCLC cell lines with wild-type BAD. Cell proliferation, cell cycle, apoptosis, and invasion were characterized in vitro. Tumorigenicity was analyzed in vivo. Western blot was performed to determine the effects of BAD overexpression on the Bcl-2 family proteins and apoptosis-related proteins.
  
  
  RESULTS
  Overexpression of BAD significantly inhibited cell proliferation in H1299, H292, and SPC-A1 but not in SK-MES-1 and H460 cell lines in vitro. BAD overexpression also reduced the tumorigenicity of H1299/SPC-A1 cell in vivo. However, no appreciable effects on cell cycle distribution and invasion were observed in all these cell lines. BAD overexpression also induced apoptosis in all cell types, in which process expression of mitochondrial cytochrom c (cyto-c) and caspase 3 were increased, whereas Bcl-xl, Bcl-2, Bax and caspase 8 expressions did not changed. These findings indicated that a mitochondrial pathway, in which process cyto-c was released from mitochondrial to activate caspase 3, was involved in BAD overexpression-mediated apoptosis.
  
  
  CONCLUSIONS
  Our data suggested that increased expression of BAD enhance apoptosis and has negative influence on cell proliferation and tumor growth in NSCLC. Bad is a new potential target for tumor interventions.
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R China.|Department of Respiratory Medicine, Nanchong Central Hospital, Nanchong 637000, P.R China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R China.
authors.forename: Man
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R China.
authors.forename: Bojiang
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R China.
authors.forename: Lin
authors.initials: L
authors.lastname: Mai
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Chengdu Medical College, Chengdu 610072, P.R China.
authors.forename: Na
authors.initials: N
authors.lastname: Huang
authors.affiliation: Clinical Laboratory Department, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, P.R China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Laboratory Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, P.R China.
authors.forename: Xianming
authors.initials: X
authors.lastname: Mo
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Li