title: Effects of Thalidomide Combined with Interferon on Inhibiting Kasumi-1 Cell Proliferation.
abstract: BACKGROUND
  Our previous clinical observations proved that the combination of thalidomide and interferon (IFN) had certain effects in relapsed or refractory AML.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effects and its mechanism of thalidomide and IFN on inhibiting the proliferation of Kasumi-1 cells.
  
  
  METHODS
  Thalidomide, IFN and a combination of both drugs were used to treat Kasumi-1 cells. The inhibition of cell proliferation and the apoptosis rate were measured. Vascular endothelial growth factor levels and the expression of apoptosis-related proteins were detected by ELISA and Western blotting, respectively.
  
  
  RESULTS
  Thalidomide and IFN could both inhibit Kasumi-1 cell proliferation in a dose-dependent manner. When Kasumi-1 cells were treated with thalidomide 350 μg/mL or IFN1400 U/mL for 48 h, the proliferation inhibition rates were (48.8 ± 4.64)% and (50.19 ± 2.59)% and the rates of apoptosis were (14.68 ± 2.61)% and (21.71 ± 0.71)%, respectively; when treated with a combination, the cell proliferation inhibition rate and apoptotic rate were statistically significantly higher than both the control group and the groups treated with a single drug. The ELISA assay revealed that both 350 μg/mL of thalidomide and 1400 U/mL of IFN could reduce the VEGF levels in cell culture supernatants; the two-drug combination group had a further decreased VEGF concentration. Forty-eighthour treatment of thalidomide 350 μg/mL and IFN 1400 U/mL could significantly decrease Bcl-2 expression and increase the expression levels of phosphor-P38, BAX, cytochrome c, and cleaved caspase-3, -8, and -9 as compared to the control group. The combination group exhibited significantly greater extents of reduction in Bcl-2 protein and increases in p-P38, BAX, and cytochrome c, and cleaved caspase-3, -8, and -9 protein expression as compared to the single drug groups.
  
  
  CONCLUSIONS
  Thalidomide and IFN can synergistically inhibit Kasumi-1 cell proliferation, which is possibly achieved through the mitochondrial and death receptor pathways and through the activation of the P38 signaling pathway to induce apoptosis and by inhibiting Kasumi-1 cell autocrine VEGF secretion.
authors.affiliation: Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Mi
authors.affiliation: Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wei
mesh_terms: D000208:Acute Disease; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D013792:Thalidomide; D045304:Cytochromes c; D007372:Interferons; D020169:Caspases
keywords: Kasumi-1 cells; acute myeloid leukemia; interferon; thalidomide