YC-1改善乏氧增强人肺腺癌A549细胞放射敏感性的体外研究

Effect of YC-1 on improving hypoxia and radiosensitizing human lung adenocarcinoma cells in vitro

目的探讨3-（5’-羟甲基-2’-呋喃基）-1-苯甲基吲唑（YC-1）对乏氧人肺腺癌A蚋细胞的放射增敏作用。方法用噻唑蓝比色法检测YC-1对细胞增殖活性的影响，以及YC-1对细胞作用24h的20％药物抑制浓度（IC20）。细胞克隆形成实验计算细胞存活分数，多靶单击模型拟合细胞存活曲线并计算放射增敏比（SER）。流式细胞仪检测细胞凋亡率和细胞周期。结果YC-1对A舛，细胞有增殖抑制作用，在-定剂量范围内呈时间-剂量依赖性。在常氧和乏氧培养24h下aIC20分别为16．7μmol／L和39．2μmol／L。乏氧加YC-1组的SERD0=1．11，SERDq=1．26。在乏氧培养下，YC-1联合单次2Gy放射能明显促进A549细胞凋亡和G2＋M期阻滞[（30．17±1．21）％：（15．44±0．96）％，P=0．000和（21．56±0．47）％：（6．16±0．16）％，P=0．000]。结论YC-1对乏氧的As49细胞有放射增敏作用。

Objective To investigate the radiosensitizing effect of 3- （5＇-hydroxy-2＇-furyl） -1-benzyl indazole （YC-1） on hypoxic human adenocarcinoma cell line A549. Methods MTT assay was used to test the inhibitory effect of YC-1 on proliferation of A549 cells. Clonogenic assay was performed to determine the radiosensitizing effect of YC-1 on hopxic A549 ceils. Single-hit multi-target model was used to plot survival curve and calculate sensitization enhancement ratio （SER）. The cell cycle and apoptosis were measured by flow cytometry. Results The proliferation of A549 ceils was inhibited by YC-1 in a time-dose-dependent manner. In normoxic and hypoxic ceils, the IC20 was 16. 7 μmol/L and 39.2 μmol/L at 24 h, respectively. In the group of hypoxia plus YC-1,SERD0 and SERDq were 1.11 and 1.26, respectively. In hypoxia, YC-1 combined with 2 Gy irradiation could induce cell apoptosis and prolong G2 ＋ M phase arrest （ （ 30.17 ± 1.21）%： （15.44 ±0. 96）% ,P=0. 000;（21.56 ±0. 47）%： （6.16±0. 16）% ,P=0. 000）. Conclusions YC-1 could enhance the radiosensitivity of hypoxic A549 ceils.