title: [Synergism of As2S2 and STI 571 in inducing apoptosis of K562 cells].
abstract: OBJECTIVE
  To investigate the synergistic effect of As(2)S(2) and STI 571 on K562 cells and its mechanism.
  
  
  METHODS
  The inhibitive effect of As(2)S(2) on the proliferation of K562 cells was determined by cell number count. Cell apoptosis was assessed by flow cytometry, DNA fragmentation and morphology. Protein expression was determined by Western-blot and gene expression by RT-PCR.
  
  
  RESULTS
  As(2)S(2) could significantly inhibit the proliferation and induce apoptosis of K562 cells in a dose and time-dependent manner at concentrations from 1 micromol/L to 5 micromol/L for 24 approximately 72 h. 34.4%, 21.8% and 46.0% of the treated-cells displayed apoptosis at 3 micro mol/L for 72 h, 5 micromol/L for 48 h and 5 micromol/L for 72 h, respectively. Compared to treatment with STI571 (0.25 approximately 1.00 micromol/L) or As(2)S(2) (1 approximately 5 micromol/L) alone, treatment of K562 cells with As(2)S(2) and STI571 combination induced more cell apoptosis. (18.4 +/- 1.4)% and (15.8 +/- 1.2)% cells underwent apoptosis at 1 micromol/L STI571 for 48 h and 5 micromol/L As(2)S(2) for 48 h, respectively, and (40.6 +/- 2.0)% cells did in combination treatment (P < 0.05). For U937 cells, the percentages of apoptotic cells were (6.0 +/- 1.1)% at 1 micromol/L STI571 for 48 h, (4.5 +/- 1.2)% at 5 micromol/L As(2)S(2) for 48 h, and (7.3 +/- 1.0)% in combination treatment. As(2)S(2) decreased the bcr-abl fusion protein expression and PTK activity of c-abl and bcr-abl, but not for bcr-abl expression.
  
  
  CONCLUSIONS
  Combination treatment with As(2)S(2) and STI 571 induced more apoptosis of K562 cells. The reduction of PTK activity may be involved in the mechanisms.
authors.affiliation: Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
authors.forename: Jun-e
authors.initials: JE
authors.lastname: Li
authors.forename: Guan-lin
authors.initials: GL
authors.lastname: Sun
authors.forename: Ying-li
authors.initials: YL
authors.lastname: Wu
authors.forename: Wei-li
authors.initials: WL
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001152:Arsenicals / Q000494:pharmacology*; D001549:Benzamides; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl