J Cancer 2020; 11(12):3667-3674. doi:10.7150/jca.42850 This issue Cite

Research Paper

Cyclooxygenase-2 mediates gefitinib resistance in non-small cell lung cancer through the EGFR/PI3K/AKT axis

Qin-fang Deng, Qi-yu Fang, Xian-Xiu Ji, Song-wen Zhou

Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China

Citation:
Deng Qf, Fang Qy, Ji XX, Zhou Sw. Cyclooxygenase-2 mediates gefitinib resistance in non-small cell lung cancer through the EGFR/PI3K/AKT axis. J Cancer 2020; 11(12):3667-3674. doi:10.7150/jca.42850. https://www.jcancer.org/v11p3667.htm
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Abstract

Gefitinib is a potent inhibitor of EGFR and represents the front-line treatment for non-small cell lung cancer (NSCLC) therapeutics. However, NSCLC patients are prone to develop acquired resistance through as yet, undefined mechanisms of resistance. Here, we investigated the role of COX-2 during gefitinib resistance in NSCLC cells and revealed its underlying mechanism(s) of action. We report the upregulation of COX-2 in gefitinib-resistant NSCLC tissues and cells, which is associated with poor prognosis. In vitro assays in NSCLC cells (PC9/GR) showed that COX-2 facilitates gefitinib resistance in NSCLC cells through its effects on P-gp, MRP1, and BCRP, and cancer cell migration and invasion. In vivo, COX-2 silencing could repress tumor growth. We found that the overexpression of COX-2 enhances the transcription of MMP-2, MMP-7, and MMP-9 which mediates PI3K-AKT activation. In summary, we demonstrate that COX-2 mediates the gefitinib resistance of NSCLC cells through its interaction with EGFR and the PI3K-AKT axis. This highlights COX-2 as a novel molecular target for NSCLC.

Keywords: non-small cell lung cancer, gefitinib resistance, COX-2, PI3K-AKT, EGFR


Citation styles

APA
Deng, Q.f., Fang, Q.y., Ji, X.X., Zhou, S.w. (2020). Cyclooxygenase-2 mediates gefitinib resistance in non-small cell lung cancer through the EGFR/PI3K/AKT axis. Journal of Cancer, 11(12), 3667-3674. https://doi.org/10.7150/jca.42850.

ACS
Deng, Q.f.; Fang, Q.y.; Ji, X.X.; Zhou, S.w. Cyclooxygenase-2 mediates gefitinib resistance in non-small cell lung cancer through the EGFR/PI3K/AKT axis. J. Cancer 2020, 11 (12), 3667-3674. DOI: 10.7150/jca.42850.

NLM
Deng Qf, Fang Qy, Ji XX, Zhou Sw. Cyclooxygenase-2 mediates gefitinib resistance in non-small cell lung cancer through the EGFR/PI3K/AKT axis. J Cancer 2020; 11(12):3667-3674. doi:10.7150/jca.42850. https://www.jcancer.org/v11p3667.htm

CSE
Deng Qf, Fang Qy, Ji XX, Zhou Sw. 2020. Cyclooxygenase-2 mediates gefitinib resistance in non-small cell lung cancer through the EGFR/PI3K/AKT axis. J Cancer. 11(12):3667-3674.

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