金属铜配合物Cu（Ⅱ）1-羟基-3-（2-环氧基）吨酮的体外抗肿瘤作用

摘要：目的探讨金属铜配合物Cu（Ⅱ）1-羟基-3-（2-环氧基）吨酮（Cu-HOX）的体外抗肿瘤作用。方法采用噻唑蓝比色法测定Cu—HOX对卵巢癌细胞3AO、食管鳞癌细胞ECA109、肺癌细胞GLC-82、胃癌细胞SGC-7901增殖的抑制作用；应用流式细胞仪检测药物对3AO细胞周期和凋亡的影响。结果Cu-HOX呈浓度依赖性的抑制3AO、ECA109、GLC-82、SGC-7901细胞生长，作用72h的半抑制浓度（IC50）依次为8．0、〉50、6．7和9．0μg／mL，其中以Cu-HOX和卡铂对3AO细胞IC50的比值最小，说明Cu—HOX对3AO的敏感性明显强于卡铂。作用24、48、72hCu—HOX呈浓度、时间依赖性的抑制3AO细胞生长，作用明显强于卡铂。3．125-25μg／mL使3AO细胞S期增加而G1期减少，引起细胞凋亡。结论Cu—HOX在体外具有抗肿瘤作用，其中对3AO细胞的敏感性最高，其机理为阻止细胞于S期和诱导细胞调亡。

Anti-tumor effects of Cu complex with 1-hydroxy-3-(2-oxirarylmethoxy) xanthone in vitro

Objective To study the antitumor effect of Cu complex with 1-hydroxy-3-（2-oxirarylmethoxy） xanthone （Cu-HOX） in vitro and the effect on 3AO cell cycle and apoptosis. Methods Cell growth inhibition effect of tumor cells after treated with Cu-HOX was determined by 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide in vitro. Cell cycle and apoptosis were determined by flow cytometry. Results Cu-HOX was inhibited 3AO, ECA109, GLC-82, SGC-7901 cells growth in a concentration dependent manner. After treatment with Cu-HOX 72 h, the 50% inhibiting concentration on 3AO, ECA109, CLC-82, SGC-7901 cells were 8.0, 〉50, 6.7 and 9.0 μg/mL, respectively. The sensitivity of Cu-HOX on 3AO cell was the highest. Its concentration and time dependence inhibited 3AO cells growth. 3.125-25 μg/mL Cu-HOX increased S phase but decreased G1 phase of 3AO cell. Meanwhile it also significantly induced 3AO cell apoptosis. Conclusion Cu-HOX have antitumor effect in vitro and 3AO cell was the most sensitive and its mechanism may be due to arrest cell in S phase and induce cell apoptosis.