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Overexpression of GPR35 confers drug resistance in NSCLC cells by β-arrestin/Akt signaling

Authors Wang W, Han T, Tong W, Zhao J, Qiu X

Received 29 May 2018

Accepted for publication 19 July 2018

Published 26 September 2018 Volume 2018:11 Pages 6249—6257

DOI https://doi.org/10.2147/OTT.S175606

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Dr Takuya Aoki


Wei Wang,1 Tianci Han,1 Wei Tong,1 Jian Zhao,1 Xueshan Qiu2

1Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, China; 2Department of Pathology, The First Hospital of China Medical University, Shenyang 110001, China

Background: Non-small-cell lung cancer (NSCLC) is the major leading cause of cancer-related death around the world. The resistance to chemotherapy limits the effects of clinical treatment. The aim of this study was to identify novel mechanisms involved in NSCLC chemoresistance.
Materials and methods: We explored the public database and commercial tissue microarray to evaluate the expression of G protein-coupled receptor 35 (GPR35). We established the chemoresistant A549 cell line to further investigate the biological function of GPR35 in vitro and in vivo. Then, we measured the altered signalings that GPR35 knocking down by Western blot assay.
Results: We demonstrated that GPR35 expression was significantly elevated in NSCLC tissues and correlated with poor prognosis. GPR35 was upregulated in our in vitro chemoresistance cell model. GPR35 depletion reduced the half maximal inhibitory concentration of chemodrugs and restored the sensitivity both in vitro and in vivo. Mechanically, we found that GPR35-mediated chemoresistance occurred partially via β-arrestin-2/Akt signaling. Furthermore, inhibition of β-arrestin-2 or Akt activation could suppress the GPR35 expression and overcome chemoresistance.
Conclusion: Our results suggested that GPR35 might serve as a novel therapeutic target to enhance the chemotherapy efficacy in NSCLC.

Keywords: GPR35, NSCLC, chemoresistance, β-arrestin-2

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