4-氨基-1,8-萘二胺对三氧化二砷在肝癌细胞中的增敏作用研究

李洋; 罗擎英; 邓建军等

4-氨基-1,8-萘二胺对三氧化二砷在肝癌细胞中的增敏作用研究

4-amino-1,8-naphthalimide on the Sensitive Effect of Arsenic Trioxide in Hepatocellular Carcinoma Cells

摘要

摘要: 目的探讨聚腺苷酸二磷酸核糖转移酶-1（PARP-1）抑制剂4-氨基-1，8-萘二胺（4-AN）对三氧化二砷（ATO）治疗肝癌的敏感性影响及其相关机制。方法培养人肝癌细胞HepG2，分为单独ATO用药组和联合用药组（4-AN+ATO），采用MTT实验、群体倍增实验和克隆形成实验比较两组细胞存活、增殖情况；应用ELISA、单细胞凝胶电泳（彗星实验）及微核实验分别检测细胞内8-羟基鸟嘌呤（8-OH-dG）含量，DNA链断裂、修复以及染色体损伤情况。结果当ATO浓度为2～10 μmol/L时，联合用药组细胞存活率和集落形成率低于ATO组（\P\P\P＜0.05）；彗星实验检测损伤修复结果显示，联合用药组细胞的DNA损伤修复效率低于ATO组（\P\P<0.05）。结论 PARP-1抑制剂4-AN能显著增强ATO杀伤肝癌细胞的敏感性，其机制与抑制肝癌细胞DNA损伤修复有关。

Abstract: Objective To study the effect and mechanism of 4-amino-1,8-naphthalimide(4-AN) on the sensitive effect of arsenic trioxide (ATO) in hepatocellular carcinoma cells. Methods Hepatocellular carcinoma HepG2 cells were divided into two groups according to whether they were treated with 4-AN or not. Cell viability was evaluated by MTT assay, population doubling experiment and colony formation assay; genic mechanism was explored by 8-OH-dG assay, single cell gel electrophoresis (comet assay) and micronucleus test. Results At 2-10 μmol/L concentration of ATO, the cell viability and colony formation efficiency of the combination group (4-AN+ATO) were significantly lower than that of the ATO group (\P\P\P\P\P<0.05). Conclusion 4-AN can significantly increase the sensitivity of ATO in treatment with hepatocellular carcinoma cells and prevent DNA damage repair may be a primary mechanism for this effect.

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