title: In vitro study of human mutL homolog 1 hypermethylation in inducing drug resistance of esophageal carcinoma.
abstract: BACKGROUND
  Aberrant promoter methylation of tumor suppressor gene can inhibit corresponding protein expression and promote carcinogenesis. Many studies have demonstrated that human mutL homolog 1(hMLH1) promoter methylation is correlated with occurrence and progression of multiple types of tumors. However, its correlation with esophageal carcinoma drug resistance is still unknown.
  
  
  OBJECTIVE
  To confirm methylation status of hMLH1 promoter in drug-resistance cell line of esophageal carcinoma, further confirm whether hMLH1 promoter methylation is responsible for drug resistance.
  
  
  METHODS
  Two stable esophageal carcinoma drug-resistance cell lines were successfully established by Cisplatin (DDP) concentration increment method; methylation status of hMLH1 promoter, mRNA and protein expression of hMLH1 were detected by methylation-specific PCR (MSP), RT-PCR and western blot, respectively; Drug-resistance ability assay was used to detect drug-resistance ability.
  
  
  RESULTS
  Stronger methylation status of hMLH1 promoter, lower hMLH1 mRNA and protein expression were found in both drug-resistance cell lines; after removing methylated bands using 5-aza-2'-deoxycytidine(5-Aza-CdR) in drug-resistance cell lines, hMLH1 mRNA and protein expression were restored and drug-resistance abilities declined nearly by half.
  
  
  CONCLUSIONS
  hMLH1 promoter hypermethylation plays important roles in esophageal carcinoma drug-resistance and show us the prospect that combination of demethylation treatment with conventional chemotherapy drugs may bring better therapy effect.
authors.affiliation: Department of Thoracic Surgery, Central Hospital of Zaozhuang Mining Group of Shandong Province, Zaozhuang, 277800, Shandong, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Thoracic Surgery, Central Hospital of Zaozhuang Mining Group of Shandong Province, Zaozhuang, 277800, Shandong, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Central Hospital of Zaozhuang Mining Group of Shandong Province, Zaozhuang, 277800, Shandong, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Second Department of Liver Failure, No. 302 Hospital of PLA, Beijing, 100000, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Oncology, Affiliated Hospital of Weifang Medical University, #465 Yu He Road, Weifang, 261000, Shandong, People's Republic of China. weifangatjinan1984@163.com.
authors.forename: G
authors.initials: G
authors.lastname: Li
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019175:DNA Methylation; D000077209:Decitabine; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D006801:Humans; D000070957:MutL Protein Homolog 1 / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D000077209:Decitabine; D000070957:MutL Protein Homolog 1; D001374:Azacitidine; D002945:Cisplatin
keywords: Drug-resistance cell line; Esophageal carcinoma; Human mutL homolog 1(hMLH1); Promoter methylation