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    PARP抑制剂Veliparib对Ishikawa子宫内膜癌细胞放疗增敏作用

    Effect of Radiosensitization of Veliparib, a Poly (ADP-ribose) polymerase (PARP) inhibitor, in Ishikawa Cells

    • 摘要: 目的 研究PARP抑制剂Veliparib对Ishikawa子宫内膜癌细胞放疗增敏作用,并探讨其可能发生机制。方法 体外培养人子宫内膜癌Ishikawa细胞,分为空白对照、Veliparib、放疗(radiotherapy, RT)、Veliparib+RT组,采用CCK-8法检测Veliparib对Ishikawa细胞10%抑制浓度(10% inhibitory concentration, IC10)值和50%抑制浓度(50% inhibitory concentration, IC50)值,克隆形成实验验证Veliparib联合放疗的体外增敏作用;Western blot检测各组DNA损伤相关蛋白γH2AX表达。结果 Veliparib对Ishikawa细胞IC10值为1.4μmol/L;IC50值为130.1μmol/L;克隆形成实验测得Veliparib放疗增敏比为1.413;Veliparib+RT组细胞中γH2AX显著高于RT组(P<0.05)。结论 研究结果表明,Veliparib对Ishikawa子宫内膜癌细胞有显著的放疗增敏作用,其机制可能与通过抑制DNA修复、增加DNA双链断裂损伤进而诱导细胞发生凋亡有关。

       

      Abstract: Objective To investigate the effect of radiosensitization of Poly (ADP-Ribose) polymerase inhibitor-Veliparib on Ishikawa cells, and to explore its potential mechanism. Methods Human endometrial carcinoma Ishikawa cells cultured in vitro were divided into four groups: Control group, Veliparib group, Radiotherapy group (RT), Veliparib combined with RT group. Cell Counting Kit-8 (CCK-8) assay was used to analyze the 10% inhibitory concentration (IC10) and 50% inhibitory concentration (IC50) of Veliparib to Ishikawa cells. The radiosensitization effect of Veliparib on Ishikawa cells was evaluated by clonogenic assay. The expression of γH2AX (DNA injury-associated protein) was observed by Western blot in vitro. Results The IC10 and IC50 value of Veliparib were 1.4 μmol/L and 130.1 μmol/L. The radio-sensitivity enhancement ratio (SER) of Veliparib combined with RT was 1.413 in vitro. Western blot results confirmed that the expression levels of γH2AX was significantly higher in the Veliparib+RT group (P<0.05). Conclusion Our in vitro data demonstrated decreased in the radiobiological effects on Ishikawa cells after addition of Veliparib to radiotherapy, which can be explained by less DNA repair, increased DNA double strand break and induction of cell apoptosis.

       

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