title: The growth-inhibitory and apoptosis-inducing effect of deferoxamine combined with arsenic trioxide on HL-60 xenografts in nude mice.
abstract: OBJECTIVE
  The aim of this study is to investigate the growth-inhibitory and apoptosis-inducing effect of deferoxamine (DFO) combined with arsenic trioxide (ATO) on the human HL-60 xenografts in nude mice and its mechanism.
  
  
  METHODS
  The highly tumorigenic leukemia cell line HL-60 cells were inoculated subcutaneously into nude mice to establish a human leukemia xenograft model. The HL-60 xenograft nude mice models were randomly divided into four groups: control (Normal saline, NS), 50mg/kg DFO, 3mg/kg ATO, the combined treatment (50mg/kg DFO+1.5mg/kg ATO) once HL-60 cells were inoculated. Tumor sizes, growth curves, inhibitory rates, cell apoptosis, and the expression of apoptosis related markers were measured to evaluate the tumor growth.
  
  
  RESULTS
  Xenografted tumors were observed in all nude mice since the 5th day of inoculation. The inhibitory rates of tumor weight were 2.67%, 10.69%, and 25.57% in DFO, ATO and combination therapy groups, respectively. The combination of DFO with ATO induces significantly more tumor cell apoptosis than either agent alone (p<0.05). The expression of NF-κBp65 and survivin proteins decreased significantly while the expression of Caspase-3 and Bax increased in the combination therapy group (p<0.05). Double immunofluorescence for Caspase-3 and NFκBp65 demonstrated an inverse relationship between Caspase-3-positive areas and NFκBp65-positive areas, as well as the co-localization of Bax and survivin in xenografted tumor cells.
  
  
  CONCLUSIONS
  Combination of DFO and ATO has synergistic effects on tumor growth inhibition and apoptosis-inducing in vivo with no significant side effects. The DFO and ATO can up-regulate the expression of Caspase-3 and Bax, and down-regulate the expression of NF-κBp65 and survivin, especially for their combination.
authors.affiliation: Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Key Discipline Laboratory of Clinical Medicine, Zhengzhou 450052, China.
authors.forename: Runhong
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Key Discipline Laboratory of Clinical Medicine, Zhengzhou 450052, China.
authors.forename: Dao
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Laboratory Medicine, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Key Discipline Laboratory of Clinical Medicine, Zhengzhou 450052, China. Electronic address: lyf6012@163.com.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects*; D003676:Deferoxamine / Q000008:administration & dosage*; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010087:Oxides / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D001152:Arsenicals; D010087:Oxides; D003676:Deferoxamine; D000077237:Arsenic Trioxide
keywords: Apoptosis; Arsenic trioxide; Deferoxamine; Leukemia; Nude mice