title: Silencing the EZH2 gene by RNA interference reverses the drug resistance of human hepatic multidrug-resistant cancer cells to 5-Fu.
abstract: OBJECTIVE
  The EZH2 gene, which is expressed in various solid tumours, including liver cancer, can regulate gene transcription and promote the generation and progression of tumours. Our aim was to investigate the relationship between EZH2 and multidrug-resistance of human hepatic cancer cells using RNA interference.
  
  
  METHODS
  We detected the expression of EZH2 in the human hepatic multidrug-resistant cancer cell line Bel/Fu by RT-PCR and western blot; then knocked EZH2 gene by RNA interference to investigate the proliferation, the cell cycle and cell apoptosis by MTT and flow cytometry; finally we checked the alteration of MDR1 methylation and MDR1 expression after EZH2 silencing by MS-PCR, RT-PCR and western blot.
  
  
  RESULTS
  EZH2 is highly expressed in Bel/Fu cells. After EZH2-depleted Bel/Fu cells were treated with 5-Fu, the cell proliferation was inhibited, the cell cycle arrested at G1, which may be associated with the alteration of G1/S checkpoint regulators, meanwhile the apoptotic rate of the cells increased. Furthermore, the expression of MDR1 decreased and the corresponding methylation levels of MDR1 were significantly increased in EZH2-depleted Bel/Fu cells.
  
  
  CONCLUSIONS
  We demonstrate the relationship between EZH2 and multidrug-resistance in hepatic cancer for the first time. EZH2 may become a new target for gene therapy to reverse multidrug-resistance in hepatic cancer.
authors.affiliation: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 410008, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guangpu
authors.initials: G
authors.lastname: Liu
authors.forename: Changwei
authors.initials: C
authors.lastname: Lin
authors.forename: Guoqing
authors.initials: G
authors.lastname: Liao
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein; D005472:Fluorouracil / Q000494:pharmacology*; D020868:Gene Silencing; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000964:Antimetabolites, Antineoplastic; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D005472:Fluorouracil