title: Proteomic studies of multiple myeloma in RPMI8226 cell line treated with bendamustine.
abstract: OBJECTIVE
  Multiple myeloma (MM) is a malignant and incurable neoplasm of plasma cells that accumulate in the bone marrow. Bendamustine, an antitumor agent including double property of alkylating agent and purine analogues, displayed clinical antitumor activity in patients with MM. However, the precise mechanism of action of bendamustine has not been completely elucidated.
  
  
  METHODS
  In this study, we established the cell model of bendamustine-induced MM RPMI8226 cell apoptosis, and used two dimensional differential in-gel electrophoresis (2D-DIGE) proteomics to analyze the bendamustine-induced protein alterations.
  
  
  RESULTS
  Our results revealed that compared with control group, bendamustine significantly inhibited the proliferation of RPMI8226 cells in a concentration-dependent and time-dependent manner. Proteomic approach was performed to identify 30 differentially expressed proteins in RPMI8226 cells upon bendamustine treatment, which included 15 up-regulated and 15 down-regulated proteins. Of these, protein disulfide isomerase A3 (PDIA3) and cytokine- induced apoptosis inhibitor 1 (CPIN1), were selected for further studies.
  
  
  CONCLUSIONS
  These results implicate PDIA3 and CPIN1 as potential molecular targets for drug intervention in MM and thus provide novel insights into the mechanisms of antitumor activity of bendamustine.
authors.affiliation: Department of Hematology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 China.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Sun
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Jingli
authors.initials: J
authors.lastname: Gu
authors.forename: Junru
authors.initials: J
authors.lastname: Liu
authors.forename: Beihui
authors.initials: B
authors.lastname: Huang
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000069461:Bendamustine Hydrochloride; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; C489114:CIAPIN1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human