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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  RUNX 3 expression significantly suppressed cisplatin resistance in Eca109 and  TE ‐1, both in vitro and vivo. Meanwhile, heterologous  RUNX 3 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  RUNX 3 expression in Eca109 and  TE ‐1. Silencing Akt1 could reverse cisplatin resistance in Eca109 and  TE ‐1.    Conclusion  Our results confirmed that a loss of  RUNX 3 in  ESCC  may contribute to cisplatin‐resistance.  RUNX 3 could reverse cisplatin resistance via suppression of the Akt pathway in  ESCC  patients.

RUNX 3 reverses cisplatin resistance in esophageal squamous cell carcinoma via suppression of the protein kinase B pathway