title: [Effect of PARP1 inhibitor PJ34 on multi-drug resistance in human multiple myeloma cell line and its relationship with FA/BRCA pathway].
abstract: OBJECTIVE
  To investigate the effect of PARP1 inhibitor PJ34 on multi-drug resistance in a human multiple myeloma cell line and its connection with FA/BRCA pathway in DNA damage repair.
  
  
  METHODS
  A CCK8 assay was used to measure the inhibition rate. Real-time quantitative PCR was used to detect expression changes of DNA repair genes involved in the FA/BRCA pathway. Western blotting assay was used to detect expression of key protein FANCD2 in the FA/BRCA pathway. Annexin VFITC/PI double staining flow cytometry was used to measure cell apoptosis induced by PJ34. A COMET assay was used to detect the effect of PJ34 on DNA damage repair.
  
  
  RESULTS
  PJ34 could significantly enhance the sensitivity of RPMI8226/R cells to melphalan. The IC50 value of melphalan was dropped from 20.43 mol/L to 7.8 mol/L. PJ34 could inhibit the DNA damage repair, and the effect was related with the inhibition of FA/BRCA pathway. PJ34 and melphalan showed a synergistic effect in promoting the apoptosis of RPMI8226/R cells.
  
  
  CONCLUSIONS
  PJ34 can reverse the resistance of RPMI8226/R cells to melphalan by inhibiting the FA/BRCA pathway, which in turn can induce suppression of DNA damage repair. Therefore, PJ34 may have clinical value in overcoming the multi-drug resistance of multiple myeloma.
authors.affiliation: Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China. Email: huixiaowh@hotmail.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Xiong
authors.forename: Heng
authors.initials: H
authors.lastname: Wei
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D024682:BRCA2 Protein; C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases