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

Effects of a PARP inhibitor veliparib on the radiotherapy sensitization of Ishikawa cells

目的研究聚腺苷二磷酸核糖聚合酶（PARP）抑制剂veliparib对lshikawa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（contr01）、veliparib、放疗（RT）、veliparib＋RT组，采用CCK-8法检测veliparib对Ishikawa细胞10％抑制浓度（IC10）值和50％抑制浓度（IC50）值，克隆形成实验验证veliparib联合放疗的体外增敏作用；Westernblot检测各组DNA损伤相关蛋白γH2AX表达。结果veliparib对Ishikawa细胞IC10值为1．7μmol／L；IC值为133．5μmol／L；克隆形成实验测得veliparib放疔增敏比为1．229；veliparib＋Rr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。

Objective To investigate the effects of a poly（ ADP - ribose） polymerase （PARP） inhibitor veliparib on the radiotherapy sensitization of human endometrial carcinoma Ishikawa cells, and to explore its potential mechanism. Methods Ishikawa cells cultured in vitro were divided into four groups： a control group, a veliparib group, a radiotherapy （RT） group, and a veliparib ＋ RT group. The cell counting kit -8 （CCK -8） assay was used to analyze the 10% inhibitory concentration （ IC10 ） and 50% inhibitory concentration （ ICs0 ） of veliparib to Ishikawa cells. The radiotherapy sensitive effects of veliparib on Ishikawa cells were evaluated by the elonogenie assay. The expression of γH2AX （ DNA injury -associated protein） was observed by Western blotting in vitro. Results The IC10 and IC50 values of veliparib were 1.7 μmol/L and 133.5μmol/L, respectively. The radio - sensitivity enhancement ratio （SER） of veliparib was 1. 229. The levels of γH2AX was significantly higher in the veliparib ＋ RT group （ P 〈 0.05 ）. Conclusions Veliparib can produce remarkable radiotherapy sensitive effects on Ishikawa cells, which may be related with inhibited DNA repair, increased DNA double strand break and induction of cell apoptosis.