title: [Effect of nuclear receptor inhibitor importazole on the proliferation and apoptosis of multiple myeloma cells].
abstract: OBJECTIVE
  To investigate the effect of nuclear receptor inhibitor importazole (IPZ) on cell cycle and apoptosis of multiple myeloma (MM) cells and its regulatory mechanisms.
  
  
  METHODS
  MM cell lines RPMI 8226 and NCI-H929 cells were treated with different concentrations of IPZ. Cell viability was detected through MTT method. Cell cycle and apoptosis were measured by flow cytometry (FCM). Nuclear NF-κBprotein expression was tested by Western blot. Electrophoretic mobility shift assay (EMSA) was used to analyze the DNA binding activity.
  
  
  RESULTS
  IPZ induced a dose- and time- dependent inhibition of myeloma cells growth. And the IC50 values of IPZ on RPMI 8226 and NCI-H929 after 48 hours incubation were (4.43±0.41) and (4.78±0.35) μmol/L, respectively, and the percentages of S phase cells decreased from (54.95±4.34)％ and (51.38±2.43)％ to (42.77±3.19)％ and (40.98±6.46)％, respectively. After treatment with IPZ at 8, 12 and 16 μmol/L, the apoptosis rate significantly increased from (2.47±0.60)％ of the control group to (14.53±0.90)%, (32.57±1.80)% and (58.3±1.9)% (P<0.05) in RPMI 8226 and from (2.37±0.70)％ of the control group to (19.46±0.70) %, (46.02±1.10) % and (60.63±1.60)% in NCI-H929, respectively. Treatment of RPMI 8226 and NCI-H929 cells with 8 μmol/L IPZ for 24 h could inhibit NF-κB import to nucleus and reduce its DNA binding activity.
  
  
  CONCLUSIONS
  The nuclear receptor inhibitor importazole inhibits proliferation and induces apoptosis of multiple myeloma cells by blocking the NF-κB signal pathway in vitro.
authors.affiliation: Department of Hematology, the Second Military Medical University, Shanghai, China.
authors.forename: Wen-qing
authors.initials: WQ
authors.lastname: Yan
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D011799:Quinazolines; C568452:importazole