In vitro radiosensitization of (E)-2'-deoxy-2'-(fluoromethylene) cytidine

Objective To investigate the radiosensitization of a new nucleoside analogue (E) 2' deoxy 2' (fluoromethylene) cytidine (FMdC) in vitro. Methods Clonogenic assay was used to investigate the radiosensitizing effect of FMdC on a human colorectal cancer cell line WiDr and two cervical cancer cell lines C33 A and C4 I. The change in radiosensitivity was quantified by calculating the sensitization enhancement ratio at a clinically relevant dose of 2?Gy (SER SF2 ), defined as the mean survival fraction (SF) for control/mean SF for FMdC. Results FMdC enhanced the radiosensitivity of WiDr cells in a time course dependent manner. After treatment with 30?nmol/L FMdC for 6～72 h, no radiosensitization was observed at 6, 12 and 24 h, whereas an enhancement of radiosensitivity was seen at 48 h and 72 h. The corresponding SER SF2 was 1.33 and 1.79, respectively. With a high dose of 300?nmol/L FMdC exposed to WiDr cells for 6, 12, and 24 h, the SER SF2 were 1.19, 1.73 and 3.5, respectively. The radiosensitizing effect was dependent on the doses of FMdC. Pre irradiation exposure of WiDr cells to 20～50?nmol/L FMdC for 48 h resulted in an increase of SER SF2 from 1.15 to 2.28. The observed radiosensitization was also confirmed on two human cervical cancer cell lines C33 A and C4 I with a SER SF2 of 1.32 and 2.08, respectively. Conclusions These results show that FMdC is a potential radiosensitizer in colorectal cancer and cervical cancer cell lines.