(E)-(2’)-脱氧-氟亚甲基胞苷的体外放射增敏作用

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

目的 观察一种新的核苷酸类似物 (E) (2’) 脱氧 氟亚甲基胞苷 (FMdC)在体外的放射增敏作用。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 FMdC增加WiDr细胞的放射敏感性 ,并呈时间依赖关系。照射前用 30nmol/LFMdC处理WiDr细胞 6～ 72h ,在 6、12和 2 4h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(30 0nmol/L)处理WiDr细胞 6、12和 2 4h ,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、1.73和 3.5 0。FMdC的放射增敏作用和药物剂量相关 ,2 0～ 5 0nmol/LFMdC处理细胞 48h ,SERSF2 从 1.15增加至 2 .2 8。用 30nmol/LFMdC处理C33 A和C4 I细胞 48h同样可观察到放射增敏作用 ,SERSF2 分别为 1.32和 2 .0 8。结论 FMdC对结肠癌和宫颈癌细胞有明显的放射增敏作用 。

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.