NU7026对肝癌细胞放射增敏作用及机制研究

Study on radiosensitization effects and mechanisms of NU7026 on hepatocellular carcinoma cells

为给研制新的抗癌和放射增敏药物提供理论依据,采用Western blot检测DNA-PKcs在肝癌细胞中的表达水平及NU7026对DNA-PKcs活性的影响,以彗星实验表达检测细胞DNA受损的情况,微核实验观察染色体损伤,克隆形成实验观察对细胞株放射敏感性的影响。结果表明,DNA-PKcs在肝癌细胞中呈高表达,NU7026能抑制辐射所诱发的p-DNA-PKcs/S2056的活化,微核实验及彗星实验检测表明,NU7026能有效延长辐照后细胞的修复时间,并能明显降低放射后细胞的克隆形成率。提示NU7026对肝癌细胞有放射增敏作用,其作用机制与抑制DNA-PKcs活性有关。

We aim to study the effect of NU7026 on the proliferation and radiosensitivity of HepG2 cells, and to provide experimental data and advanced evidence for exploring anticancer and radiation sensitizing new drugs. Western blot was used to detect expression level of DNA-PKcs in HepG2 cells and the activity of p-DNA-PKcs/S2056 inhibited by NU7026. The DNA damage was judged by the expression level of 7-H2AX. The micronucleus experiment was taken to observe chromosome damage; clonogenic assay was performed to determine the radiosensitizing effect of NU7026. The results show that DNA-PKcs is highly expressed in HepG2 cells, NU7026 reduce the expression of p-DNA-PKcs/S2056 micro nuclear test and 7-H2AX test shows NU7026 could effectively prolong the time of DNA repair after irradiation, and significantly reduce cloning efficiency of ceils induced by radiation. It can be concluded that NU7026 can enhance the radiation sensitivity of HepG2 cells and its mechanism may be related to inhibition of DNA-PKcs activity.