title: [Efficacy of combination treatment of the inhibitor of phosphatidyl inositol-3-kinase/protein kinase B pathway BEZ235 and the inhibitor of extracellular regulated protein kinase/mitogen-activated protein kinase pathway U0126 in a tumor cell model].
abstract: OBJECTIVE
  To study the inhibitory effect of the dual usage of BEZ235 and U0126, the inhibitor of phosphatidyl inositol-3-kinase/protein kinase B pathway and extracellular regulated proteinkinase/mitogen-activated protein kinase pathway, respectively, on cell proliferation.
  
  
  METHODS
  Phosphatase and tensin homolog knockout mouse embryonic fibroblast (PTEN-/-MEF) cell lines were used as the cellular model for malignant tumors. BEZ235, the dual inhibitor of phosphatidyl inositol-3-kinase and mammalian target of rapamycin, and U0126, the inhibitor of mitogen-activated protein kinase were used to treat the cells individually and in a combination manner. The inhibitory effects to cell proliferation were monitored by MTT.
  
  
  RESULTS
  Both BEZ235 and U0126 suppressed PTEN knockout cell proliferation, and their half inhibitory concentrations were 6.257 nmol/L and 22.85 μmol/L, respectively. However, the combination treatment of the two drugs showed antagonistic rather than synergistic effect on cell proliferation.
  
  
  CONCLUSIONS
  BEZ235 and U0126 are not suitable for a combined target therapy regimen.
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, CAMS and PUMC, Beijing 100005, China.
authors.forename: Xin-xin
authors.initials: XX
authors.lastname: Chen
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Yu-zhuo
authors.initials: YZ
authors.lastname: Shi
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004336:Drug Antagonism; D005347:Fibroblasts / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009570:Nitriles / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines / Q000494:pharmacology*
chemical_list: D002070:Butadienes; D007093:Imidazoles; D009570:Nitriles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines; C113580:U 0126; D058539:Phosphatidylinositol 3-Kinase; C531198:dactolisib