(E)-(2’)-脱氧-氟亚甲基胞苷的体外放射增敏作用

目的：观察一种新的核苷酸类拟物（E）－（2')－脱氧－氟亚甲基胞苷（FMdC)在体外的放射增殖作用。方法：在结肠癌（WiDr)和宫颈癌（C33－A和C4－I）细胞系进行克隆形成试验。常规照射剂量2Gy时的放射增敏比（SERSF2）定义为2Gy时对照组存活份数（SF）和药物处理组SF之比。结果MFdC增加WiDr细胞的放射敏感性，并呈时间依赖关系。照射前用30nmol/L FMdC处理WiDR细胞-72h，在6、12和24h未能观察到放射增敏作用，放射增敏作用仅在48和72h出现，其SERSF2分别为1．33和1．79。当高剂量FMdC(300nmol/L)处理WiDr细胞6、12和24h，各时间点均可见放射增敏效应。相应的放射增敏比SERSF2分别为1．19、173和3．50。FMDdC的放射增敏作用和药物剂量相关，20－50nmol/L FMdC处理细胞48h,SERSF2从1．15增加至2．28。用30nmol/L FMdC处理C33－A和C4－I细胞48h同样观察到放射增敏作用，SERSF2分别为1．32和2．08。结论FMdC对结肠癌和中颈癌细胞有明显的放射增敏作用，与时间和剂量相关。

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 (SERSF2), 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 SERSF2 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 SERSF2 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 SERSF2 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 SERSF2 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.