Selective nuclear export inhibitor KPT‑330 enhances the radiosensitivity of esophageal carcinoma cells.

Abstract

Although the concurrent application of definitive chemoradiation has improved the prognosis of patients with esophageal cancer, resistance to therapy poses a major threat to treatment. The present study aimed to investigate whether the use of KPT-330, a selective inhibitor of nuclear export (SINE), enhances the radiosensitivity of esophageal cancer cells. Immunohistochemical staining assays were employed to evaluate the expression and prognostic significance of chromosome maintenance protein-1 (CRM1) in 111 esophageal carcinoma (ESCA) tissues collected from patients with esophageal squamous cell carcinoma. The data showed that the expression of CRM1 in the ESCA tissues was significantly upregulated compared with that in the normal adjacent tissues. Furthermore, patients with higher CRM1 expression had significantly decreased overall survival compared with those with lower CRM1 expression. The effects of KPT-330 and/or radiation on ECA109 human ESCA cells were also evaluated. KPT-330 suppressed the viability of the ECA109 cells. A colony formation assay demonstrated that a combination of KPT-330 and radiation significantly decreased ECA109 cell proliferation. Flow cytometric analysis showed that KPT-330 increased the arrest of the ECA109 cells at the G2/M phase and induced apoptosis. In addition, western blotting revealed that the inhibitory effect of KPT-330 on cell viability was associated with the increased expression of p53 and promotion of the nuclear accumulation of the p53 protein. In conclusion, the present study demonstrated that CRM1 expression is associated with the prognosis of patients with ESCA following radiotherapy. The inhibition of CRM1 expression by the SINE inhibitor KPT-330 increases radiosensitivity and is potentially useful in a combination treatment strategy for esophageal cancers.