title: [Phosphorylation of eukaryotic initiation factor 2-alpha inhibits cisplatin-mediated apoptosis of hepatocellular carcinoma cells].
abstract: OBJECTIVE
  To investigate whether the phosphorylation (functionally inhibitive) of eukaryotic initiation factor 2-alpha (eIF2-a) affects the molecular mechanism of cisplatin-induced cellular apoptosis in human hepatocellular carcinoma (HCC).
  
  
  METHODS
  The human HCC cultured cell lines SMMC-7221 and HepG2 were treated with cisplatin alone (controls; 24 h) or in combination with pre-transfection of a dominant-negative eIF2-a mutant (eIF2aS51A) or pre-exposure to an eIF2-a-specific phosphatase inhibitor (salubrinal) to decrease or increase the phosphorylation level, respectively. Changes in expression of apoptosis markers were quantitatively and qualitatively assessed by flow cytometry and western blot analysis. The significance of differences among groups was assessed by analysis of variance testing and of differences between groups was assessed by t-test.
  
  
  RESULTS
  Cisplatin treatment induced the appropriate functional-inhibitive phosphorylation of eIF2-a on serine 51. Cisplatin treatment (10 mg/ml) induced significant apoptosis in the eIF2aS51A pre-transfected SMMC-7721 (control: 21.7 +/- 1.5% vs. 50.7 +/- 2.1%, t = 19.454, P less than 0.05) and HepG2 (21.0 +/- 1.0% vs. 57.3 +/- 2.1%, t = 27.250, P less than 0.05). Salubrinal pre-treatment significantly inhibited the cisplatin (15 mg/ml)-induced apoptosis in SMMC-7721 (control: 50.3 +/- 2.5% vs. 16.3 +/- 2.1%, t = 18.031, P less than 0.05) and HepG2 (42.0 +/- 2.6% vs. 12.0 +/- 2.0%, t = 15.667, P less than 0.05).
  
  
  CONCLUSIONS
  Phosphorylation of eIF2-a may act to inhibit cisplatin-induced apoptosis of HCC.
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Hospital of Luzhou Medical College, Luzhou Sichuan province 646000, China.
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Feng
authors.forename: Run
authors.initials: R
authors.lastname: Chen
authors.forename: Shao-Kun
authors.initials: SK
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Duan
authors.forename: You-Ping
authors.initials: YP
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Rong-Yang
authors.initials: RY
authors.lastname: Dai
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms; D010766:Phosphorylation
chemical_list: D015852:Eukaryotic Initiation Factor-2; D002945:Cisplatin