title: Phosphatidylinositol 3-kinase inhibitor LY294002 suppresses proliferation and sensitizes doxorubicin chemotherapy in bladder cancer cells.
abstract: BACKGROUND
  Phosphatidylinositol 3-kinase (PI3K)-AKT signaling is a well-characterized pathway involved in the control of cell proliferation, apoptosis and oncogenesis. LY294002 is a commonly used pharmacologic inhibitor which acts at the ATP-binding site of the PI3K enzyme, thus selectively inhibiting the PI3K-AKT nexus. The purpose of the present study was to examine whether PI3K inhibited by LY294002 had an effect on human bladder cancer cells.
  
  
  METHODS
  After treatment with LY294002, MTT assay, chemosensitivity test, colony formation assay, apoptosis assay and Western blot analysis were conducted in EJ cells.
  
  
  RESULTS
  EJ cells treated with LY294002 showed significant AKT phosphorylation suppression in a dose-response manner. Also, PI3K/AKT signaling inhibitor LY294002 suppressed cell proliferation and enhanced the chemosensitivity of doxorubicin in human bladder cancer EJ cells. Furthermore, LY294002 increased cell apoptosis to doxorubicin.
  
  
  CONCLUSIONS
  The augmentation of doxorubicin with PI3K inhibitor LY294002 may resolve the multidrug resistance of bladder cancer, and this may be a new strategy for achieving tolerance for chemotherapeutic agents in bladder cancer therapy.
authors: Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Deyao
authors: D
authors: Wu
authors: Jun
authors: J
authors: Tao
authors: Bin
authors: B
authors: Xu
authors: Weijie
authors: W
authors: Qing
authors: Pengchao
authors: P
authors: Li
authors: Qiang
authors: Q
authors: Lu
authors: Wei
authors: W
authors: Zhang