title: [Effects of fludarabine on apoptosis and gene expression profile in multiple myeloma cells].
abstract: OBJECTIVE
  To investigate the in vitro effects of fludarabine on apoptosis and gene expression profile in human multiple myeloma (MM) cells.
  
  
  METHODS
  Cell growth was measured by a MTT assay. Cells apoptosis was evaluated by flow cytometry. The activation of caspase cascade was determined by Western blot analysis. The expression profile of apoptosis-related genes in human MM cells was detected by cDNA expression array system.
  
  
  RESULTS
  The growth of RPMI8226 and KM3 cells was suppressed by fludarabine treatment in a dose and time-dependent manner. After treatment with fludarabine for 24 h, the IC(50) for RPMI8226 cells was 2.13 µg/ml, and 0.36 µg/ml for KM3 cells. Apoptotic cells of RPMI8226 and KM3 increased in a dose- dependent manner after exposure to fludarabine for 24 h. Western blot analysis showed the activation of caspase-3 and PARP in the MM cells treated with fludarabine. The cDNA expression array showed that multiple pathways were involved in the apoptosis induced by fludarabine. Among 97 apoptosis-related genes, 25 genes were differently expressed and 13 expressions were up-regulated in fludarabine treated group, involving in Bcl-2 pro-apoptotic gene, tumor necrosis factor (TNF) and its receptor superfamily gene, and caspase recruitment domain family, 12 genes expression down-regulated, including Bcl-2 antiapoptotic gene, TNF superfamily and its receptor related factor gene and apoptosis inhibitor protein family.
  
  
  CONCLUSIONS
  Fludarabine can significantly inhibit MM cell growth and induce apoptosis in vitro. The multiple pathways may be involved for the apoptosis in MM cells.
authors.affiliation: The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Yang
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Meng
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Qian
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D059467:Transcriptome
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3