title: 5-azacytidine reverses drug resistance in bladder cancer cells.
abstract: BACKGROUND
  Patients with metastatic and muscle-invasive bladder cancer are commonly treated with cisplatin. A significant proportion of patients develop disease progression after an initial response to chemotherapy. Presently there is no standard of care for such patients. We examined whether pretreatment with an epigenetic agent would result in reversal of drug resistance.
  
  
  METHODS
  Methylation of proapoptotic and cell cycle genes in bladder cancer cells was examined. Cisplatin- and docetaxel-resistant cells were generated. The effect of target of methylation-induced silencing (TMS1) expression and pretreatment of wild-type and drug-resistant cells with 5-azacytidine on chemosensitivity was determined.
  
  
  RESULTS
  Unidirectional crossresistance of cisplatin-resistant UMUC3 cells to docetaxel was observed. Recombinant expression of TMS1 or pre-treatment of wild-type and drug-resistant cells with 5-azacytidine resulted in enhanced sensitivity to cisplatin and docetaxel.
  
  
  CONCLUSIONS
  Our results indicate that epigenetic therapy may restore sensitivity to chemotherapeutic agents in bladder cancer cells.
authors: Sylvester Cancer Center, University of Miami, FL, USA.
authors: Kavitha
authors: K
authors: Ramachandran
authors: Edna
authors: E
authors: Gordian
authors: Rakesh
authors: R
authors: Singal
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000494:pharmacology*; D015153:Blotting, Western; D053468:CARD Signaling Adaptor Proteins; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D043823:Taxoids / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000964:Antimetabolites, Antineoplastic; D053468:CARD Signaling Adaptor Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; C402202:PYCARD protein, human; D012333:RNA, Messenger; D043823:Taxoids; D025521:Tumor Suppressor Proteins; D000077143:Docetaxel; D001374:Azacitidine; D002945:Cisplatin