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 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, and thus selectively inhibits the PI3K-AKT nexus. The purpose of the study was to examine whether PI3K inhibited by LY294002 had effects in human bladder cancer cells.
  
  
  METHODS
  After treatment with LY294002, MTT assay, a 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 suppressing in a dose-response manner. Additionally, the PI3K/AKT signaling inhibitor LY294002 suppressed cell proliferation and enhanced chemosensitivity to doxorubicin in human bladder cancer EJ cells. Furthermore, LY294002 increased cell apoptosis to doxorubicin.
  
  
  CONCLUSIONS
  The augmentation of doxorubicin with the 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.affiliation: Department of Urology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, China.
authors.forename: Deyao
authors.initials: D
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Weijie
authors.initials: W
authors.lastname: Qing
authors.forename: Pengchao
authors.initials: P
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002867:Chromones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020128:Inhibitory Concentration 50; D009025:Morpholines / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004317:Doxorubicin; D051057:Proto-Oncogene Proteins c-akt; C022616:thiazolyl blue