title: [A dual PI3K/mTOR inhibitor, PI-103, cooperates with TRAIL in laryngeal squamous carcinoma cells in vitro].
abstract: OBJECTIVE
  To investigate the effects of a dual phosphoinosmde-3-kinase (PI3K)/ mammalian target of rapamycin (mTOR) inhibitor, PI-103, cooperating with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the laryngeal squamous carcinoma Hep-2 cells.
  
  
  METHODS
  Hep-2 cells were divided into 7 groups: LY294002 group, Rapamycin group, PI-103 group, LY294002+ TRAIL group, Rapamycin+ TRAIL group, PI-103+ TRAIL group and control group.The cell cycle and apoptosis of Hep-2 cells were assessed by flow cytometry.For PI-103 group, PI-103+ TRAIL group and control group, migration and invasion ability were measured by transwell migration and invasion assay respectively.The expression of relative proteins in apoptosis and PI3K/AKT/mTOR signal pathway was examined by Western blotting.
  
  
  RESULTS
  Combination of PI-103 and TRAIL could make cell cycle arrest at S phase (G1: 1.80%±0.30%; G2: 0.00), inhibit cell proliferation, and enhance apoptosis (66.78%±2.93%) (P<0.05). Combination of PI-103 and TRAIL could statistically decrease the migration and invasion number of Hep-2 cells (17.0±3.4, 18.4±5.4) than that of PI-103 group (41.2±3.8, 41.6±4.7). PI-103 could inhibit PI3K/AKT/mTOR signal pathway by decreasing the protein expression of p-AKT and p-4E-BP1.Comparing with the control group, the expression of cysteinyl aspartate specific proteinase (Caspase) 9, 8, 3 were increased while the expression of Cyclin D1, Cyclin E1, p-AKT, p-4E-BP1 were decreased in PI-103 and PI-103+ TRAIL group (P<0.05).
  
  
  CONCLUSIONS
  Enhanced anti-tumor effects was observed by combination of PI-103 and TRAIL on laryngeal cancer cells in vitro and this combined administration might be a promising strategy for clinical treatment of laryngeal cancer.
authors.affiliation: Department of Otorhinolaryngology, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai 200031, China.
authors.forename: C L
authors.initials: CL
authors.lastname: Gao
authors.forename: K N
authors.initials: KN
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.forename: L
authors.initials: L
authors.lastname: Tao
authors.forename: M
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002867:Chromones; D019938:Cyclin D1; D019927:Cyclin E; D005663:Furans; D006258:Head and Neck Neoplasms; D006801:Humans; D007822:Laryngeal Neoplasms; D009025:Morpholines; D015513:Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D011725:Pyridines; D011743:Pyrimidines; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D053221:TNF-Related Apoptosis-Inducing Ligand; D058570:TOR Serine-Threonine Kinases
chemical_list: D002867:Chromones; D019938:Cyclin D1; D019927:Cyclin E; D005663:Furans; D009025:Morpholines; D015513:Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D011725:Pyridines; D011743:Pyrimidines; D053221:TNF-Related Apoptosis-Inducing Ligand; D058570:TOR Serine-Threonine Kinases; C530104:CCND1 protein, human; C475820:CCNE1 protein, human; C522973:PI103; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human