Effect of combined treatment with radiation and low dose etoposide on cell survival

Background: To improve the radiotherapy results, we evaluated etoposide as an effective radiosensitizer by using cultured cell-lines. Materials and Methods: Four cell lines having different doubling times (DT) were used: V79 (Chinese hamster fibroblasts, DT=9 hours), (1), T24 (human bladder cancer, DT=19 hours) (2), MDA-MB231 (human breast cancer, DT=25-30 hours) (3) and RMG1 (human ovarian cancer, DT=50 hours) (4). Cell survival was determined by colony assay and cell cycle analysis was performed by flow-cytometry. Results; The survival curves showed RMG1 to be the most radiosensitive, followed by MDA-MB231, T24, and V79. V79 was most chemosensitive to etoposide, followed by T24, MDA-MB231 and RMG1. Neither 24-hours exposure to etoposide (≤0.05 μg/ml) or 0.5-h exposure (≤1.0 μg/ml) had any cell killing effect on any of the cell lines used. When the cells were irradiated after exposure to 1 μg/ml of etoposide for 0.5 hours, no radiosensitization was observed in any of the cell lines except V79. Enhanced radiosensitivity was observed in V79 and T24 cells (which have a relatively short DT) when they were incubated with 0.05 μg/ml etoposide for 24 hours but no enhanced effect was seen in MDA-MB231 or RMG1 cells (which have a relatively long DT). Conclusion: It is suggested that a combination of radiation and etoposide may be useful in the treatment of rapidly growing cancer.