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Selective COX-2 inhibitor celecoxib combined with EGFR-TKI ZD1839 on non-small cell lung cancer cell lines: in vitro toxicity and mechanism study

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Abstract

Constitutive expression of cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) occurs frequently in non-small cell lung cancer (NSCLC). Anticancer research targeting EGFR has got an extensive attention especially in NSCLC and COX-2 inhibitor also shown a certain anticancer activity in recent years. Simultaneously targeting COX-2 and EGFR may be a promising therapeutic way. We carried out the in vitro study using selective COX-2 inhibitor celecoxib combined with EGFR-tyrosine kinase inhibitor (EGFR-TKI) ZD1839 on NSCLC cell lines to investigate the anti proliferation effect and the cell molecular mechanism. MTT growth assay showed the synergistic therapeutic effect of certain concentration of celecoxib combined with ZD1839 and synergistic apoptosis effect was detected by Hoechest33258 fluorescence staining and flow cytometric analysis. In western blot analysis, ZD1839 single agent inhibited the activation of EGFR and downstream cell signal transduction AKT and extrocellular signal-regulated kinase (ERK) pathways, the transcription activity of nuclear factor-kappa B (NF-κB), and the expression of COX-2. Celecoxib single agent could also inhibit AKT and ERK pathway in NSCLC, even the EGFR expression under high concentration treatment. Celecoxib combined with ZD1839 led to stronger inhibition of related cell signal transduction pathways in NSCLC.

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Abbreviations

COX-2:

Cyclooxygenase-2

FAP:

Familial adenomatous polyposis

EGFR:

Epidermal growth factor receptor

NSCLC:

Non-small cell lung cancer

EGFR-TKI:

EGFR-tyrosine kinase inhibitor

ERK:

Extrocellular signal-regulated kinase

NF-κB:

Nuclear factor-kappa B

PGE2:

Prostaglandin E2

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Acknowledgments

We thank a lot Pro. Liwu Fu for detailed instructions, critical comments, and technology support.

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Authors and Affiliations

  1. Internal Department of Cancer Center, Sun Yat-sen University, Guang Zhou, Guang Dong, China

    Likun Chen, Youjian He, He Huang & Hai Liao

  2. Thoracic Department of Cancer Center, Sun Yat-sen University, Dongfeng Road, East, 651#, Guang Zhou, Guang Dong, 510060, China

    Weidong Wei

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  1. Likun Chen
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Correspondence to Weidong Wei.

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Chen, L., He, Y., Huang, H. et al. Selective COX-2 inhibitor celecoxib combined with EGFR-TKI ZD1839 on non-small cell lung cancer cell lines: in vitro toxicity and mechanism study. Med Oncol 25, 161–171 (2008). https://doi.org/10.1007/s12032-007-9015-1

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