Open AccessRUNX 3 reverses cisplatin resistance in esophageal squamous cell carcinoma via suppression of the protein kinase B pathway
Author(s) -
Li Dejun,
Shi Mo,
Wang Zhou
Publication year - 2016
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.12370
Subject(s) - cisplatin , medicine , cancer research , protein kinase b , ectopic expression , gene silencing , heterologous , chemotherapy , apoptosis , oncology , cell culture , biology , gene , biochemistry , genetics
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.