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HER2 induces cell proliferation and invasion of non-small-cell lung cancer by upregulating COX-2 expression via MEK/ERK signaling pathway

Authors Chi F, Wu R, Jin X, Jiang M, Zhu X

Received 11 September 2015

Accepted for publication 28 November 2015

Published 5 May 2016 Volume 2016:9 Pages 2709—2716

DOI https://doi.org/10.2147/OTT.S96197

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati


Feng Chi, Rong Wu, Xueying Jin, Min Jiang, Xike Zhu

Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China

Abstract: HER2 positivity has been well studied in various cancers, but its importance in non-small-cell lung cancer (NSCLC) is still being explored. In this study, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect HER2 and COX-2 expression in NSCLC tissues. Then, pcDNA3.1-HER2 was used to overexpress HER2, while HER2 siRNA and COX-2 siRNA were used to silence HER2 and COX-2 expression. MTT assay and invasion assay were used to detect the effects of HER2 on cell proliferation and invasion. Our study revealed that HER2 and COX-2 expression were upregulated in NSCLC tissues and HER2 exhibited a significant positive correlation with the levels of COX-2 expression. Overexpression of HER2 evidently elevated COX-2 expression, while silencing of HER2 evidently decreased COX-2 expression. Furthermore, overexpressed HER2 induced the ERK phosphorylation, and this was abolished by the treatment with U0126, a pharmacological inhibitor of MEK, an upstream kinase of ERK. HER2-induced expression and promoter activity of COX-2 were also suppressed by U0126, suggesting that the MEK/ERK signaling pathway regulates COX-2 expression. In addition, HER2 induced activation of AKT signaling pathway, which was reversed by pretreatment with U0126 and COX-2 siRNA. MTT and invasion assays revealed that HER2 induced cell proliferation and invasion that were reversed by pretreatment with U0126 and COX-2 siRNA. In this study, our results demonstrated for the first time that HER2 elevated COX-2 expression through the activation of MEK/ERK pathway, which subsequently induced cell proliferation and invasion via AKT pathway in NSCLC tissues.

Keywords: HER2, MEK/ERK, COX-2, AKT signaling pathway, non-small-cell lung cancer

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