• Pulm Pharmacol Ther · Jun 2014

    β-Catenin overexpression is associated with gefitinib resistance in non-small cell lung cancer cells.

    • Xia Fang, Pan Gu, Caicun Zhou, Aibin Liang, Shenxiang Ren, Fang Liu, Yu Zeng, Yunjin Wu, Yinmin Zhao, Binbin Huang, Zongmei Zhang, and Xianghua Yi.
    • Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: dilay_123@yahoo.cn.
    • Pulm Pharmacol Ther. 2014 Jun 1; 28 (1): 41-48.

    BackgroundAcquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) presents great challenges in the treatment of non-small cell lung cancer (NSCLC) patients, while the mechanisms are still not well understood. The β-catenin signaling pathway has been found to be associated with chemoresistance and can activate the EGFR and its downstream pathways. This study aimed to investigate the role of β-catenin in acquired resistance to EGFR-TKIs in NSCLC cell lines.MethodsThe expression and transcriptional activity of β-catenin were measured in both the NSCLC cell line PC9 and its sub-line PC9/AB(2) which has acquired resistance to gefitinib. Knockdown and overexpression of β-catenin in the PC9/AB(2) and PC9 cells were performed. The cell survival rate and the activation of the EGFR and its downstream pathways were detected in the two cell lines after transfection.ResultsNuclear translocation of β-catenin was increased in the PC9/AB(2) cells and the baseline expression of members of the β-catenin signaling pathway was also higher in the PC9/AB(2) cells. Knocking down the expression of β-catenin increased the sensitivity of the PC9/AB(2) cells to gefitinib by blocking the activation of the EGFR downstream pathways, while β-catenin overexpression improved PC9 cells resistance to gefitinib by enhancing the activation of the EGFR and its downstream signaling.Conclusionβ-catenin plays an important role in acquired resistance to EGFR-TKIs in NSCLC cell lines and may be a potential therapeutic target for NSCLC patients who have failed to respond to targeted therapy.Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

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