title: [Effects of As2O3 on the Proliferation, Differentiation and Apoptosis of HL-60 Cells and Its Related Mechanisms].
abstract: OBJECTIVE
  To investigate the effects of arsenic trioxide (As2O3) on the proliferation, differentiation and apoptosis of HL-60 cells in vitro and explore the underlying mechanisms.
  
  
  METHODS
  After HL-60 cells were treated with different concentration of As2O3, the cell proliferation was determined by MTS/PES method, the differentiation state was detected by the nitroblue tetrazolium (NBT) reduction test; flow cytometry was used to analyze the apoptosis and expression of CD11b. In addition, SYBR Green real-time RT-PCR was used to measure the mRNA levels of C-FES, BCL-2, BAX, survivin , P21 and P27.
  
  
  RESULTS
  As2O3 could obviously inhibit the proliferation of HL-60 cells, and the effect was in dose- and time-dependent manners (r=-0.967; r=-0.954). Low concentration (0.1, 0.5 and 1.0 µmol/L) of As2O3 could significantly promote the differentiation of HL-60 cells, the cells exhibited a higher NBT-reducing ability and expressed far more CD11b antigens. High concentration (2.5 and 5.0 µmol/L) of As2O3 induced HL-60 cell apoptosis, but the ability of promoting differentiation decreased. The expression of C-FES mRNA significantly increased after being treated with As2O3 at the concentrations 1.0 and 5.0 µmol/L, and the former is more obvious, which confirmed that C-FES mRNA level paralleled the cell differentiation degree. Also, the expression of BCL-2 and survivin significantly decreased, while the expression of BAX, P21 and P27 was significantly upregulated in HL-60 cells after being treated with 5.0 µmol/L As2O3.
  
  
  CONCLUSIONS
  As2O3 can significantly suppress cell proliferation, promote the differentiation and induce the apoptosis in HL-60 cells, and the mechanism of As2O3 anti-tumor activity may be involved in the regulation of C-FES, cell cycle and apoptosis-related genes.
authors.affiliation: Department of Laboratory Medicine, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China.
authors.forename: Jin-Hai
authors.initials: JH
authors.lastname: Ren
authors.affiliation: Department of Laboratory Medicine, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Cui
authors.affiliation: Department of Laboratory Medicine, Peking University Third Hospital, Beijing 100191, China. E-mail: bjmuzhangjie@sina.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals; D002454:Cell Differentiation; D049109:Cell Proliferation; D018922:HL-60 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins; D010087:Oxides
chemical_list: D001152:Arsenicals; D008869:Microtubule-Associated Proteins; D010087:Oxides; D000077237:Arsenic Trioxide