title: [Study on matrine alleviating retinoic acid resistance in acute promyelocytic leukemia].
abstract: OBJECTIVE
  To explore the role of matrine (MAT) alleviating all-trans retinoic acid (ATRA) resistance in acute promyelocytic leukemia (APL) and its mechanism.
  
  
  METHODS
  ATRA sensitive strain of APL (NB4) and resistant strain (NB4-R1, NB4-R2) were used in this study. The low toxic dosage of MAT was established by MTT test, and ATRA IC(50) of the cell strains (cultured with or without 0.1 mmol/L MAT) were obtained to confirm the reversal index (RI); the influence of MAT (10, 8, 6, 4, 2, 1, 0.1, 0.01, 0.001 mmol/L) combine with 1 µmol/L ATRA on the differentiation of the three cell strains were observed by nitro blue tetrazolium chloride (NBT) test and morphologic changes. The apoptosis rate of cells treated with different concentration of MAT combined with 1 µmol/L ATRA was tested by flow cytometry with Annexin V/PI staining.
  
  
  RESULTS
  (1) The toxicity of MAT to NB4, NB4-R1, and NB4-R2 cells was increased with the concentration, IC(50) value was (0.661 ± 0.035) mmol/L, (0.673 ± 0.132) mmol/L and (0.329 ± 0.020) mmol/L, respectively; (2) After treated with 0.1 mmol/L MAT, the ATRA resistance factor of NB4-R1 decreased markedly (RI = 4.96 ± 1.15), but did not of NB4-R2(RI = 0.66 ± 0.17); (3) The differentiation capacity of NB4 and NB4-R1 was enhanced with increase of MAT, and peaked at 0.1 mmol/L (P < 0.05), but did not of NB4-R2; (4) After treated with MAT, the ATRA (1 µmol/L) induced apoptosis rate in NB4 and NB4-R1 increased significantly (P < 0.05 and P < 0.01, respectively).
  
  
  CONCLUSIONS
  MAT can reverse the ATRA resistance of NB4-R1, which may relate to the effect of MAT on differentiation and apoptosis. Treatment with MAT plus ATRA may exaggerate the cells resistance potency.
authors: Hematology Department of TCM Hospital of Zhejiang Province, Hangzhou 310006, China.
authors: Di-jiong
authors: DJ
authors: Wu
authors: Yu-hong
authors: YH
authors: Zhou
authors: Jun
authors: J
authors: Zhu
authors: Wei
authors: W
authors: Zhao
authors: Wei-jun
authors: WJ
authors: Zhong
authors: Zhen
authors: Z
authors: Wang
authors: Huan
authors: H
authors: Qian
authors: Rui
authors: R
authors: Li
authors: Shan
authors: S
authors: Fu
authors: Jie
authors: J
authors: Sun
mesh_terms: D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D011807:Quinolizines / Q000494:pharmacology* / Q000627:therapeutic use; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D011807:Quinolizines; D014212:Tretinoin; D000093842:Matrines