ARRB1 enhances the chemosensitivity of lung cancer through the mediation of DNA damage response

Shen,Hongchang; Wang,Liguang; Zhang,Jiangang; Dong,Wei; Zhang,Tiehong; Ni,Yang; Cao,Hongxin; Wang,Kai; Li,Yun; Wang,Yibing; Du,Jiajun

doi:10.3892/or.2016.5337

February-2017 Volume 37 Issue 2

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February-2017 Volume 37 Issue 2

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Article Open Access

ARRB1 enhances the chemosensitivity of lung cancer through the mediation of DNA damage response

Authors:
- Hongchang Shen
- Liguang Wang
- Jiangang Zhang
- Wei Dong
- Tiehong Zhang
- Yang Ni
- Hongxin Cao
- Kai Wang
- Yun Li
- Yibing Wang
- Jiajun Du
View Affiliations / Copyright

Affiliations: Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China, Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China

Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 761-767
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Published online on: December 28, 2016

https://doi.org/10.3892/or.2016.5337
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Abstract

ARRB1 (also known as β-arrestin-1) serves as a multifunctional adaptor contributing to the regulation of signaling pathways. ARRB1 may be involved in DNA damage accumulation; however the underlying mechanism involved is unclear. In the present study, non-small cell lung cancer (NSCLC) cell lines (H520 and SK-MES-1) were transfected with ARRB1 plasmids or small interfering ribonucleic acid (siRNA) and received treatment with DNA-damaging agents (cisplatin and etoposide). A mouse xenograft model was used to assess the impact of ARRB1 on the efficacy of cisplatin in vivo. A total of 30 surgically resected NSCLC patients were recruited for the present study and qRT-PCR was performed to determine the mRNA levels in cancer tissues compared with para-carcinoma tissues. Our data showed that DNA damage was abrogated in the ARRB1‑knockdown cells and enhanced in the ARRB1-overexpressing cells. ATR and Chk1 were more activated in the ARRB1-overexpressing cells compared to the ARRB1-knockdown cells, followed by increased H2AX phosphorylation. DNA damage and apoptosis were increased in the ARRB1-overexpressing cells treated with cisplatin. These data provided strong evidence that ARRB1 contributes to the response of NSCLC to DNA-damaging agents and is essential for DNA damage response (DDR). ARRB1 may enhance the efficacy of DNA-damaging agents in NSCLC.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

ARRB1 enhances the chemosensitivity of lung cancer through the mediation of DNA damage response

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Abstract

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