title: Paclitaxel-Fe3O4 nanoparticles inhibit growth of CD138(-) CD34(-) tumor stem-like cells in multiple myeloma-bearing mice.
abstract: BACKGROUND
  There is growing evidence that CD138(-) CD34(-) cells may actually be tumor stem cells responsible for initiation and relapse of multiple myeloma. However, effective drugs targeted at CD138(-) CD34(-) tumor stem cells are yet to be developed. The purpose of this study was to investigate the inhibitory effect of paclitaxel-loaded Fe3O4 nanoparticles (PTX-NPs) on CD138(-) CD34(-) tumor stem cells in multiple myeloma-bearing mice.
  
  
  METHODS
  CD138(-) CD34(-) cells were isolated from a human U266 multiple myeloma cell line using an immune magnetic bead sorting method and then subcutaneously injected into mice with nonobese diabetic/severe combined immunodeficiency to develop a multiple myeloma-bearing mouse model. The mice were treated with Fe3O4 nanoparticles 2 mg/kg, paclitaxel 4.8 mg/kg, and PTX-NPs 0.64 mg/kg for 2 weeks. Tumor growth, pathological changes, serum and urinary interleukin-6 levels, and molecular expression of caspase-3, caspase-8, and caspase-9 were evaluated.
  
  
  RESULTS
  CD138(-) CD34(-) cells were found to have tumor stem cell characteristics. All the mice developed tumors in 40 days after injection of 1 × 10(6) CD138(-) CD34(-) tumor stem cells. Tumor growth in mice treated with PTX-NPs was significantly inhibited compared with the controls (P < 0.005), and the groups that received nanoparticles alone (P < 0.005) or paclitaxel alone (P < 0.05). In addition, the PTX-NPs markedly inhibited interleukin-6 secretion, increased caspase-8, caspase-9, and caspase-3 expression, and induced apoptosis of tumor cells in the treated mice.
  
  
  CONCLUSIONS
  PTX-NPs proved to be a potent anticancer treatment strategy that may contribute to targeted therapy for multiple myeloma tumor stem cells in future clinical trials.
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Nanjing, People’s Republic of China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Dengyu
authors.initials: D
authors.lastname: Chen
authors.forename: Junsong
authors.initials: J
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Xiong
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry*; D016019:Survival Analysis; D053668:Syndecan-1 / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D053668:Syndecan-1; D020169:Caspases; D017239:Paclitaxel
keywords: Fe3O4 nanoparticles; multiple myeloma; paclitaxel; tumor stem cells