三氧化二砷对纤维肉瘤细胞放射增敏作用的研究

Radiation enhancement on fibrosarcoma cells by arsenic trioxide

目的研究和探讨三氧化二砷(As_2O_3)是否对纤维肉瘤细胞有放射增敏作用。方法以人纤维肉瘤细胞HT1080为实验对象,首先检测As_2O_3的单药毒性,确定IC_(10)、IC_(50)和IC_(90)。放射增敏作用的实验分为空白对照组、单纯给药组、单纯照射组(包括1、2、4、6、8、10Gy剂量)、照射前加药组(于照射前24h加入设定浓度的As_2O_3,药物作用24h后进行照射)和照射后加药组(于照射后即刻加入设定浓度的As_2O_3,药物作用24h)。所有实验均重复3次。采用克隆形成分析法观察单纯照射和照射联合As_2O_3对细胞的杀伤作用。计算细胞的存活分数,用多靶单击模型进行拟合并做图。结果HT1080细胞的IC_(10)、IC_(50)和IC_(90)剂量分别为0．57、3．67和12．0μmol/L。无毒剂量的As_2O_3照射前给药增敏比(SER)为0．86(Do值比)、0．98(SF_2值比),照射后给药SER为0．99(Do值比)、1．09 (SF_2值比)。IC_(50)剂量的As_2O_3,照射前给药SER为0．90(Do值比)、0．87(SF_2值比),照射后给药SER为1．14(Do值比)、1．08(SF_2值比)。IC_(90)剂量的As_2O_3照射前给药和照射后给药的SER均为1．14(Do值比)、3．20(SF_2值比),As_2O_3对低剂量照射的放射增敏作用好于高剂量照射(SER_(SF_2)＞SER_(Do))。结论As_2O_3对HT1080纤维肉瘤细胞具有一定的放射增敏作用,为临床放疗和As_2O_3联合应用提供了实验依据。

Objective To study the radio-sensitizing effect of arsenic trioxide（ As203 ） in human fibrosarcoma cells. Methods Human fibrosarcoma cells HT1080 was selected for this study. The toxic effect of As2O3 was examined to define the CI10, CI50 and CI90 in HT1080 cells. The cells were treated in vitro with different doses of radiation alone or radiation combined with As2O3 administrated before and after radiation. Colony forming assay was used for cellular survival fraction analysis. Single-hit muhitarget model was used to plot the survival curve. Results The IC10, IC50 and IC90 of As2O3 in HT1080 cells was 0.57, 3.67 and 12.0 μmol/L, respectively. Sensitization enhancement ratio（SER） were 0.86 and 0.98 according to Do and SF2 value when As2 03 was administrated at nontoxic dose before radiation. They were 0.99 and 1.09 after radiation. SER were 0.90 and 0.87 according to Do and SF： value when As2O3 was administrated at IC50 dose before radiation, they were 1.14 and 1.08 after radiation. SER were 1.14 and 3.20 according to Do and SF2 value when As2O3 was administrated at IC90 dose before and after radiation. Conclusion As2O3 is shown as possessing a radiosensitizing effect in vitro in HT1080 fibrosarcoma cells.