In Vitro Radiosensitization by Eribulin in Human Cancer Cell Lines
Abstract Objectives: To determine the radiosensitizing properties of eribulin and to establish the potential mechanisms of radiosensitization in cervical (HeLa) and pharyngeal (FaDu) cancer cell lines.Material and Methods: Cytotoxicity was evaluated by the crystal violet method. The 10% and 50% inhibitory concentration (IC10, IC50) for 24-hour drug exposure were determined in both cell lines. The surviving fraction at 2Gy (SF2) and the sensitizer enhancement ratio (SER) were calculated from radiation cell survival curves in presence or absence of eribulin. Combination index (CI) was calculated to determine if there is a true synergistic interaction between eribulin and irradiation. Cell cycle changes were assessed by propidium iodide staining and flow cytometry analysis. Apoptotic cells were detected by FITC-conjugated annexin-V labelling and flow cytometry and by immunofluorescence with TUNEL-assay.Results: Mean IC50s and IC10s were 1.58nM and 0.7nM and 0.7nM and 0.27nM for HeLa and FaDu cells respectively. Radiosensitization was observed in both lines tested with a SER up to 2.71 and 2.32 for HeLa and FaDu cells respectively. A true synergistic effect was showed with a CI of 0.82 and 0.76 for HeLa and FaDu cells respectively. Eribulin induced significant G2/M cell arrest and marked apoptosis. Irradiation combined with 3nM eribulin enhanced radiation induced apoptosis in Hela cells.Conclusions: Eribulin shows a true in vitro radiosensitizing effect in tested cell lines by inducing significant G2/M phase arrest and apoptosis changes. Further studies are needed to assess the clinical benefits of concurrent eribulin and radiotherapy as a novel therapeutic strategy for cancer.