title: [Inducing Effect of Akt Kinase Inhibitor MK2206 on Apoptosis in U937 Cells and RS4;11 Cells, and Its Mechanism].
abstract: OBJECTIVE
  This study was purposed to investigate the effect of Akt kinase inhibitor MK2206 on proliferation and apoptosis of U937 cells and RS4;11 cells, and to explore its possible mechanism.
  
  
  METHODS
  U937 and RS4;11 cells were cultured with different concentrations of MK2206 for 24 h and 48 h, and cell growth curve was analyzed by CCK-8; cell apoptosis was analyzed by Annexin V/7-AAD double labeling; cell cycle changes were analyzed by flow cytometry. The BAX, BCL-2, XIAP, CDK1, caspase-3 mRNA expressions were determined by real time PCR.
  
  
  RESULTS
  MK2206 significantly inhibited the growth of U937 and RS4;11 cells in a time-and dose-dependent manner, and the IC50 values of U937 cells for 24 h and 48 h were (0.48±0.15) µmol/L and (0.09±0.01) µmol/L respectively, while IC50 values of RS4;11 cells for 24 h and 48 h were (0.91±0.02) µmol/L and (0.68±0.11) µmol/L respectively. U937 were cultured with 0.5 µmol/L MK2206 and RS4;11 cells were cultured with 1.0 µmol/L MK2206 for 24 h and 48 h, and the both apoptosis rates were higher for 24 h or 48 h than that in control group (P<0.05), meanwhile the apoptosis rates for 48 h were higher than 24 h. The results of cell cycle detection showed that the both cells were arrested in G2/M phase compared with control group. The real time PCR assay revealed that the expressions of BAX, caspase-3 mRNA in cells treated with MK2206 were increased, while BCL-2, XIAP, CDK1 were reduced compared with control group.
  
  
  CONCLUSIONS
  MK2206 can inhibit proliferation and induce apoptosis of U937 and RS4;11 cells, and the both cells are arrested in G2/M phase. The mechanism of promoting apoptosis may be related with up-regulating BAX, caspase-3 and down-regulating BCL-2, XIAP, meanwhile the cell cycle arrested in G2/M phase may be associated with down-regulating CDK1.
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College; Transplantation Immunology Laboratory of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College; Transplantation Immunology Laboratory of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College; Transplantation Immunology Laboratory of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Fan-Jing
authors.initials: FJ
authors.lastname: Meng
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College; Transplantation Immunology Laboratory of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College; Transplantation Immunology Laboratory of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China. E-mail: lihmd@163.com.
authors.forename: Kai-Lin
authors.initials: KL
authors.lastname: Xu
mesh_terms: D017209:Apoptosis; D053148:Caspase 3; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006575:Heterocyclic Compounds, 3-Ring; D006801:Humans; D047428:Protein Kinase Inhibitors
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; C548887:MK 2206; D047428:Protein Kinase Inhibitors; C505407:CASP3 protein, human; D053148:Caspase 3