Poly (ADP-ribose) polymerase-1 inhibition decreases proliferation through G2/M arrest in esophageal squamous cell carcinoma

Yamamoto,Masaaki; Yamasaki,Makoto; Tsukao,Yukiko; Tanaka,Koji; Miyazaki,Yasuhiro; Makino,Tomoki; Takahashi,Tsuyoshi; Kurokawa,Yukinori; Nakajima,Kiyokazu; Takiguchi,Shuji; Mori,Masaki; Doki,Yuichiro

doi:10.3892/ol.2017.6334

Poly (ADP-ribose) polymerase-1 inhibition decreases proliferation through G2/M arrest in esophageal squamous cell carcinoma

Authors:
- Masaaki Yamamoto
- Makoto Yamasaki
- Yukiko Tsukao
- Koji Tanaka
- Yasuhiro Miyazaki
- Tomoki Makino
- Tsuyoshi Takahashi
- Yukinori Kurokawa
- Kiyokazu Nakajima
- Shuji Takiguchi
- Masaki Mori
- Yuichiro Doki
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Affiliations: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565‑0871, Japan
Published online on: June 7, 2017 https://doi.org/10.3892/ol.2017.6334
Pages: 1581-1587
Copyright: © Yamamoto et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Poly (ADP-ribose) polymerase-1 (PARP1) plays a vital role in DNA repair and is expected to be an effective target in various malignancies. The aim of the present study was to investigate the clinical and biological significance of PARP1 expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical (IHC) staining was used to examine the association between PARP1 expression and the clinicopathological features of 86 patients with ESCC. The antitumor effect of small interfering RNA against PARP1 (siPARP1) was examined in a proliferation assay, and the mechanisms of this effect were investigated using western blot analysis and cell cycle assays. Cox multivariate analysis revealed that high expression of PARP1 in IHC staining was a statistically significant independent prognostic factor of poor overall survival (OS). The adjusted hazard ratio for OS in the group with high expression of PARP1 was 2.39 (95% confidence interval, 1.29‑4.44; P=0.0051). In vitro assays showed that siPARP1 significantly decreased proliferation through G2/M arrest. Furthermore, western blot analysis showed that PARP1 was associated with the ataxia telangiectasia mutated-checkpoint kinase 2‑cell division control 25c pathway. The present study suggests that PARP1 expression has a critical role in ESCC progression, and may be a clinical therapeutic target.

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