title: [Combination of Homoharringtonine with Arsenic Trioxide Induces Apoptosis of Human Acute Myeloid Leukemia Cell Line U937].
abstract: OBJECTIVE
  To investigate the effects and mechanisms of the combination of homoharringtonine (HHT) with arsenic trioxide(As2O3) on human myeloid cell line U937 in vitro.
  
  
  METHODS
  MTT method was used to determine the antiproliferating effect of different concentrations of HHT, As2O3and their combination on U937 cells; the flow cytometry with Annexin-V-FITC/PI double staining was used to determine the apoptosis-induced effect of HHT and As2O3alone or their combination; Western blot method was used to detect the protein expression of P-AktSer473,P-AktThr308,BCL-XL, BID,MCL-1,P-MCL-1 and so on.
  
  
  RESULTS
  HHT and As2O3could significantly inhibit proliferation of U937 cells and induce their apoptosis. The combination of these 2 drugs could significantly enhance the early apoptosis of U937 cells. After combination of these 2 drugs was used, the protein expressions of P-AktSer473,P-AktThr308,MCL-1,P-MCL-1 and BCL-XL were obviously down-regulated, but the expression of BID protein did not change.
  
  
  CONCLUSIONS
  The combination treatment of HHT and As2O3can synergistically inhibit the growth of U937 cells through inhibition of PI3K/Akt signal way and MCL-1 protein.
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Department of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Department of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Department of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China.
authors.forename: Pei-Dong
authors.initials: PD
authors.lastname: You
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Department of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Department of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Central Laboratory, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China. E-mail: Huanghuif@126.com.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals; D006248:Harringtonines; D000077863:Homoharringtonine; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010087:Oxides; D019869:Phosphatidylinositol 3-Kinases; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D006248:Harringtonines; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010087:Oxides; D000077863:Homoharringtonine; D019869:Phosphatidylinositol 3-Kinases; D000077237:Arsenic Trioxide