title: RUNX3 reverses cisplatin resistance in esophageal squamous cell carcinoma via suppression of the protein kinase B pathway.
abstract: BACKGROUND
  Preoperative chemoradiation combined with surgery has been of focus recently in order to improve prognosis in esophageal squamous cell carcinoma (ESCC) patients. Finding biological markers that may assist in predicting the therapeutic effect of chemoradiation may benefit the treatment effect. In this study, the role of RUNX3 in the formation of cisplatin resistance in ESCC was examined.
  
  
  METHODS
  The study enrolled 103 stage IIa-IIIb ESCC patients who had undergone esophagectomy. RUNX3 expression in ESCC tissue was detected.
  
  
  RESULTS
  A higher expression of RUNX3 in ESCC patients correlated with a more sensitive response to cisplatin-based chemotherapy. A consistently lower expression of RUNX3 was found in the ESCC tissues of patients who agreed to perioperative chemotherapy compared with patients who had undergone no preoperative treatment. A lower RUNX3 expression in cisplatin-resistant ESCC cell lines, Eca109 and TE-1, was observed compared with parental cell lines. Heterologous RUNX3 expression significantly suppressed cisplatin resistance in Eca109 and TE-1, both in vitro and vivo. Meanwhile, heterologous RUNX3 expression could inhibit growth and induce apoptosis in cisplatin resistant Eca109 and TE-1 cell lines in vitro. Remarkable inhibition of the Akt pathway was observed in heterologous RUNX3 expression in Eca109 and TE-1. Silencing Akt1 could reverse cisplatin resistance in Eca109 and TE-1.
  
  
  CONCLUSIONS
  Our results confirmed that a loss of RUNX3 in ESCC may contribute to cisplatin-resistance. RUNX3 could reverse cisplatin resistance via suppression of the Akt pathway in ESCC patients.
authors.affiliation: Department of ICU, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: De-Jun
authors.initials: DJ
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D000077277:Esophageal Squamous Cell Carcinoma; D016629:Esophagectomy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin
keywords: 
  Akt1; 
  RUNX3
  ; cisplatin-resistanceesophageal squamous cell carcinoma