An investigation of fludarabine as a potential radiation sensitizer of human prostate cancer cells in vitro

Aim: Patient relapse following radiotherapy for prostate cancer is of major concern to oncologists. As chemotherapeutic agents have shown promise as radiation sensitizers, we investigated the use of fludarabine monophosphate as a radiation enhancement agent in human LNCaP‐LN3, PC3 and LNCaP prostate carcinoma cell lines with different sensitivities to fludarabine and ionizing radiation. Methods: Cells were treated with non‐cytotoxic doses of fludarabine for 16 h pre‐irradiation or 5 days post‐irradiation; survival fractions were determined by clonogenic assay. Cell cycling was also assessed. Results: LNCaP‐LN3 cells incubated with 1 μmol/L fludarabine for 5 days post‐irradiation were slightly sensitized (1.18 times, P = 0.029), whilst 16 h pre‐incubation had no effect on the radiation response. PC3 cells incubated with 10 μmol/L fludarabine for 16 h pre‐irradiation were sensitized to ionizing radiation (1.61 times, P < 0.0001), but treatment for 5 days post‐irradiation with fludarabine had no effect on their radiosensitivity. Neither fludarabine incubation had any effect on the sensitivity of LNCaP cells to ionizing radiation. A characterization of the cell cycle following 16 h exposure to fludarabine demonstrated that enhanced radiosensitivity of PC3 cells is independent of cell cycle. Conclusion: PC3, but not LN3 or LNCaP cells, were sensitized to ionizing radiation by pre‐incubation with 10 μmol/L fludarabine for 16 h (1.61 times, P < 0.0001) but not by post‐irradiation exposure to the drug. The enhanced radiosensitivity of PC3 cells is independent of cell cycle. Further studies are required to elucidate the mechanism of fludarabine mediated sensitization in these cells.