title: [Effects of interferon-gamma combined with all-trans retinoic acid on proliferation and differentiation of leukemia cell lines NB4 and MR2].
abstract: OBJECTIVE
  More than 90% patients with acute promyelocytic leukemia (APL) achieve clinical complete remission by using all-trans retinoic acid (ATRA). However, the rapid development of ATRA-resistance has become a problem in treating APL. Many researches indicate that the mechanism of ATRA-resistance is related to lack of some proteins synthesized by interferon (IFN). This study was to explore the possibility and the possible mechanism of treating ATRA-resistant APL with IFN in combination with ATRA.
  
  
  METHODS
  Interferon-gamma (IFNgamma) alone or IFNgamma combined with ATRA was used to treat ATRA-sensitive cell line NB4 and ATRA-resistant cell line MR2. Cell proliferation was tested by MTT assay. Light microscope and NBT test were used to evaluate cell differentiation. The expression of promyelocytic leukemia (PML) protein was observed by indirect immune fluorescent method.
  
  
  RESULTS
  On the 8th day, the growth inhibition rates of NB4 cells and MR2 cells were significantly higher in combination group than in IFNgamma group and ATRA group (95.2% vs. 68.0% and 85.0%, P<0.05; 51.5% vs. 24.1% and 4.3%, P<0.05). On the 3rd day, the positive rates of NBT in NB4 cells and MR2 cells were significantly higher in combination group than in IFNgamma group and ATRA group (93.3% vs. 19.3% and 74.7%, P<0.05; 31.5% vs. 16.8% and 5.2%, P<0.05). After treatment of IFNgamma, the fluorescent particles in NB4 and MR2 cell nuclei were obviously increased as compared with those in control group.
  
  
  CONCLUSIONS
  IFNgamma and ATRA have synergistic inhibitory effect on the proliferation of NB4 cells and MR2 cells, and can partially induce the differentiation of ATRA-resistant MR2 cells.
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P. R. China.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: He
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Rui-Bo
authors.initials: RB
authors.lastname: Cai
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D014212:Tretinoin; D007371:Interferon-gamma