title: [Effect of proteasome inhibitor bortezomib on proliferation, apoptosis and XIAP expression in K562 cells].
abstract: OBJECTIVE
  To investigate the effect of proteasome inhibitor bortezomib on proliferation, apoptosis of K562 cells and the expression of XIAP.
  
  
  METHODS
  K562 cells were treated with bortezomib at different concentration. Cell proliferation was analyzed by WST-1 assay, cell apoptosis by flow cytometry and TUNEL, XIAP mRNA expression from 5 - 100 nmol/L by RT-PCR, and XIAP protein expression by SP immunohistochemistry.
  
  
  RESULTS
  K562 cells were treated with bortezomib at different concentrations for 24 h respectively, the cells growth was significantly inhibited with inhibition rates from (13. 6 ± 0. 2)% to (81. 4 ± 0. 1)%, respectively, being markedly higher than that of control (1. 2 ± 0. 1)% (P < 0.05). IC(50) was 24. 6 nmol/L of bortezomib treated for 24 h. When K562 cells were treated with 30 nmol/L of bortezomib for 12 - 48 h, the inhibition rates were (29. 1 ± 0. 9)% to (59. 8 ± 1. 2)%, respectively, the differences being statistically significant (P < 0.05) between 12 h group and 24 h group, while there was no statistical difference between 24 h, 36 h and 48 h groups. K562 cells treated with 30 nmol/L bortezomib for 24 h showed nuclear condensation, nuclear margination, nuclear fragmentation, cytoplasmic vacuoles and a large number of apoptotic body formation. The apoptotic cells rate was 83. 67% in bortezomib treated group, and 2. 33% in untreated group (P < 0.05). The expression of XIAP mRNA was decreased in a dose-dependent manner, and the expression of its protein was down-regulated.
  
  
  CONCLUSIONS
  Bortezomib can inhibit the proliferation of K562 cells, and induce apoptosis by down-regulating the expression of XIAP, providing the laboratory evidence for the targeted therapy in acute leukemia.
authors.affiliation: Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shao
authors.forename: Ling
authors.initials: L
authors.lastname: Sun
authors.forename: Xue-yan
authors.initials: XY
authors.lastname: Cui
authors.forename: Xue-fei
authors.initials: XF
authors.lastname: Han
authors.forename: Sheng-mei
authors.initials: SM
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ling
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D000069286:Bortezomib