title: [Significance of PLSCR1 in Matrine Induced Differentiation of ATRA Resistant APL Cells].
abstract: OBJECTIVE
  To observe the expression of phospholipid scramblase 1 (PLSCR1) in matrine (MAT) induced differentiation of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) cells, and to explore its correlation to cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signal pathway.
  
  
  METHODS
  NB4 (an APL cell line sensitive to ATRA) and NB4-R1 (a resistant strain of ATRA) were observed as subjects in this study. Effects of combined treatment of 0.1 mmol/L MAT and 1 [mol/L ATRA on the differentiation of two cell lines were detected using nitroblue tetrazolium (NBT) reduction test and flow cytometry (CD11b). Expressions of PML/RARot and PLSCR1 protein/gene were detected using Western blot and Real-time fluorescence quantitative PCR assay. Meanwhile, H89, PKA antagonist, was used to observe cell differentiation antigen and changes of aforesaid proteins and genes.
  
  
  RESULTS
  MAT combined ATRA could significantly elevate positive rates of NBT and CD11 b in NB4-R1 cells, and significantly down-regulate the expression of PML/RARapha-fusion protein/gene (P < 0.05, P < 0.01). ATRA used alone could obviously enhance the expression of PLSCRI in NB4 cells at protein and mRNA levels (P < 0.01). But the expression of PLSCR1 was up-regulated in NB4-R1 cells, but with statistical.difference only at the protein level (P <0. 01). In combination of MAT, PLSCR1 protein expression was further elevated in the two cell lines (P < 0.01). Besides, there was statistical difference in mRNA expressions in NB4-R1 cells (P < 0.05). All these actions could be reversed by treatment of 10 micromol/L H89 (P < 0.05, P < 0.01).
  
  
  CONCLUSIONS
  MAT combined ATRA could significantly induce the differentiation of NB4-R1 cells, and inhibit the expression of PML/RARalpha fusion gene/protein, which might be associated with up-regulating PLSCR1 expression.
authors.forename: Di-jiong
authors.initials: DJ
authors.lastname: Wu
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Liu
authors.forename: Qi-hao
authors.initials: QH
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Ke-ding
authors.initials: KD
authors.lastname: Shao
authors.forename: Bao-dong
authors.initials: BD
authors.lastname: Ye
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Zhou
mesh_terms: D000470:Alkaloids; D000970:Antineoplastic Agents; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D011807:Quinolizines; D012333:RNA, Messenger; D015398:Signal Transduction; D014212:Tretinoin; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; C493422:PLSCR1 protein, human; D049294:Phospholipid Transfer Proteins; D011807:Quinolizines; D012333:RNA, Messenger; D014212:Tretinoin; D000093842:Matrines