Abstract

Radiotherapy remains an important treatment option for both surgical and non-surgical breast cancer patients; however resistance to radiation results in tumor recurrence and metastasis. eEF2K has been reported to play a critical role in cancer development and progression, but little is related to its radiosensitization effect. This study aimed to evaluate the radiosensitization effect of NH125, an eukaryotic elongation factor 2 kinase inhibitor, in breast cancer MDA-MB-231 and MCF-7. Cell proliferation rate was evaluated by Cell Counting Kit 8 assay. Cell cycle distribution and apoptosis rate were detected by flow cytometry. Radiosensitization ratio was evaluated by clonogenic survival assay. DNA damage repair was detected by immunofluorescent assay. Tumor-bearing xenografts confirmed the radiosensitization effect in vivo. NH125 potently sensitized MDA-MB-231 and MCF-7 to radiation with sensitization enhancement ratios 1.29 and 1.43 respectively. NH125 enhanced the radiosensitization through abrogation of G2 checkpoint and prolongation of DNA damage repair. Above all, these results demonstrated that NH125 may be a promising radiosensitizer in breast cancer radiotherapy.

Keywords: NH125, eEF2K, Eukaryotic elongation factor 2 kinase, Breast cancer, Radiosensitivity