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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 whether arsenic trioxide (As_2O_3) has radiosensitization effect on fibrosarcoma cells. Methods The human fibrosarcoma cell line HT1080 was used as the experimental object. The single-drug toxicity of As 2 O 3 was detected firstly and the IC_ (10), IC_ (50) and IC_ (90) were determined. Radiosensitization experiments were divided into blank control group, simple administration group, simple irradiation group (including 1, 2, 4, 6, 8 and 10 Gy dose), before irradiation group Of As_2O_3, 24h after irradiation), and after irradiation, the drug-added group (As_2O_3 added at the set concentration immediately after irradiation). All experiments were repeated 3 times. The colony formation assay was used to observe the cytotoxicity of As2O3 alone and irradiation. The survival score of the cells was calculated and fitted with a multi-target click model and plotted. Results The IC 10, IC 50 and IC 90 doses of HT1080 cells were 0.57, 3.67 and 12.0 μmol / L, respectively. The sensitization ratio (SER) was 0.86 (Do value ratio), 0.98 (SF 2 value ratio) before administration of non-toxic dose of As 2 O 3, the SER was 0.99 (Do value ratio) .09 (SF_2 value ratio). As_2O_3 with dose of IC 50, the SER of 0.90 (Do value ratio), 0.87 (SF_2 value ratio) were given before irradiation, and the SER after irradiation was 1.14 (Do value ratio), 1.08 (SF_2 value ratio). The SER of 1.90 (Do value ratio) and 3.20 (SF2 value ratio) of administration before and after administration of IC_ (90) As_2O_3 before irradiation and As_2O_3 were better than those of low dose radiation High dose irradiation (SER_ (SF_2)> SER_ (Do)). Conclusion As 2 O 3 has a radiosensitizing effect on HT1080 fibrosarcoma cells, providing an experimental basis for the combination of clinical radiotherapy and As 2 O 3.