title: [Synergistic effect of targeted inhibition of MEK/ERK and PI3K/AKT survival signaling pathways on induction of apoptosis in melanoma].
abstract: OBJECTIVE
  The treatment of metastatic melanoma by conventional chemotherapeutic agents remains unsatisfactory. The present study was undertaken to reveal the role of co-inhibition of survival signaling pathways in apoptosis of melanoma cells.
  
  
  METHODS
  A panel of human melanoma cell lines and fresh melanoma isolates was assessed for their sensitivity to the MEK inhibitor U0126 and/or AKT inhibitor LY294002. The proliferation and apoptosis of the cells were examined after treatment with the inhibitors.
  
  
  RESULTS
  Constitutive activation of ERK1/2 and AKT was closely related to concentrations of serum in the culture medium (extracellular signals). The sensitivity of melanoma cells to apoptosis induced by inhibition of MEK/ERK was not correlated with the active BRAF mutation (BRAF(V600E)). Inhibition of MEK/ERK predominantly induced apoptosis; whereas inhibition of PI3K/AKT primarily inhibited proliferation. Co-inhibition of MEK/ERK1/2 and PI3K/AKT synergistically induced apoptosis.
  
  
  CONCLUSIONS
  Co-targeting MEK/ERK and PI3K/AKT pathways may further improve treatment for melanoma.
authors.forename: Xin-yuan
authors.initials: XY
authors.lastname: Wang
authors.forename: Yao
authors.initials: Y
authors.lastname: Cheng
authors.forename: Ji-pei
authors.initials: JP
authors.lastname: Du
authors.forename: De-gao
authors.initials: DG
authors.lastname: Chen
authors.forename: Xue-shan
authors.initials: XS
authors.lastname: Yang
authors.forename: Zhi-mei
authors.initials: ZM
authors.lastname: Yang
authors.forename: Ning
authors.initials: N
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D002070:Butadienes; D002867:Chromones; D009025:Morpholines; D009570:Nitriles; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt