title: DNMT inhibitors and HDAC inhibitors regulate E-cadherin and Bcl-2 expression in endometrial carcinoma in vitro and in vivo.
abstract: BACKGROUND
  The effect of histone deacetylase inhibitors (HDACIs) and DNA methyltransferase inhibitors (DNMTIs) on proliferation of endometrial cancer (EC) cells in vitro and in vivo was investigated.
  
  
  METHODS
  Changes in methylation of the CDH1 promoter in HDACI- and DNMTI-treated HEC-1-B and RL-952 EC cells were detected. Nude mice with xenografted implants of human EC HEC-1-B cells were treated with valproic acid (VPA) and decitabine (DAC) and evaluated for tumor growth, CDH1 and Bcl-2 mRNA levels.
  
  
  RESULTS
  DAC, VPA and suberoylanilide hydroxamic acid (SAHA) inhibited proliferation, induced cell cycle arrest and enhanced the apoptotic index in both cell lines, DAC, VPA and SAHA upregulated E-cadherin mRNA and protein levels and downregulated Bcl-2 mRNA levels in vitro. DAC and VPA inhibited tumor growth, upregulated CDH1 mRNA and downregulated Bcl-2 mRNA levels in vivo.
  
  
  CONCLUSIONS
  A combination of HDACIs and DNMTIs suppresses the growth of EC, which is likely mediated by upregulation of E-cadherin and downregulation of Bcl-2.
authors.affiliation: Obstetrics and Gynecology Department, First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Tie-Zhong
authors.initials: TZ
authors.lastname: Yi
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Quanxin
authors.initials: Q
authors.lastname: Qu
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.forename: Hai-Di
authors.initials: HD
authors.lastname: Sun
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Tan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000188:drug therapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019175:DNA Methylation; D000077209:Decitabine; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D014635:Valproic Acid; D000077209:Decitabine; D004248:DNA (Cytosine-5-)-Methyltransferases; D001374:Azacitidine