Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint
Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint
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DOI：
10.1016/j.bbrc.2013.10.134
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发表时间：
2013-11-29
影响因子：
3.1
通讯作者：
Koizumi, Fumiaki
中科院分区：
文献类型：
--
作者：
Nakadate, Yusuke;Kodera, Yasuo;Koizumi, Fumiaki
聚（ADP-核糖）糖水解酶（PARG）是一种在聚（ADP-核糖）（PAR）降解中发挥作用的主要酶。据报道，PARG 缺陷会使细胞对辐射的影响变得敏感。然而，在肺癌中，这一点尚未完全阐明。在这里，我们使用 8 个肺癌细胞系研究了 PARG siRNA 是否有助于增加放射敏感性。其中，PARG的沉默在5种细胞系中诱导了放射增敏作用。 PC-14 和 A427 细胞中的 PARG siRNA 在很大程度上抑制了辐射诱导的 G2/M 期停滞，这些细胞对 PARG 敲低的反应表现出显着增强的放射敏感性。另一方面，在H520细胞中没有观察到类似的效果，其没有表现出放射增敏作用。与细胞周期分析一致，当用 PARG siRNA 处理时，辐射诱导的检查点信号在 PC-14 和 A427 细胞中没有被很好地激活。这些结果表明，PARG 敲低引起的对辐射的敏感性增加是通过消除肺癌细胞中辐射诱导的 G2/M 停滞和检查点激活而发生的。我们的研究结果表明，当与放疗结合使用时，PARG 可能成为肺癌治疗的潜在靶点。 (C) 2013 Elsevier Inc. 保留所有权利。
Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy. (C) 2013 Elsevier Inc. All rights reserved.