eEF2K promotes progression and radioresistance of esophageal squamous cell carcinoma

Abstract

Objectives: To investigate the biological function of eEF2K in esophageal squamous cell carcinoma (ESCC).

Materials and methods: Tissue microarrays containing 100 pairs of ESCC tumor and adjacent normal tissues were completed. Overexpression and knockdown of eEF2K were constructed in ECA-109 and TE-13 ESCC cells. DNA damage, cell viability, migration and invasion, radioresistance, apoptosis and autophagy were determined by immunofluorescence, CCK-8, transwell assay, colony formation assay, flow cytometry and western blot, respectively. Tumor growth and radioresistance were also evaluated using xenograft models created in nude mice.

Results: eEF2K expression was higher in ESCC tissues compared with matched non-tumor tissues (P<0.05). Proliferation was increased in eEF2K overexpressing cells compared with controls (P<0.05), while silencing eEF2K reduced cell proliferation (P<0.05). Furthermore, lower levels of eEF2K expression correlated with slower migration and invasion rates (P<0.05), while higher levels of eEF2K expression with faster migration and invasion rates (P<0.05). eEF2K overexpression resulted in radioresistance and radiation-induced autophagy, and reduced radiation-induced apoptosis compared with controls, but silencing eEF2K promoted radiosensitivity and apoptosis, and reduced autophagy. In addition, eEF2K overexpression promoted the tumor growth in vivo (P<0.01). Combined treatment of NH125 (a pharmacological inhibitor of eEF2K) and radiation was more effective at delaying xenograft tumor growth than NH125 and radiation alone (P<0.05).

Conclusion: eEF2K induced progression and radioresistance in ESCC, which may be a novel therapeutic target for ESCC to increase radiosensitivity.

Keywords: Apoptosis; Autophagy; Esophageal squamous cell carcinoma; Eukaryotic elongation factor 2 kinase; Radiosensitivity; Tumor growth.