國家衛生研究院 NHRI:Item 3990099045/12916
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12916


    Title: Omega-3 fatty acid-enriched fish oil and selenium combination modulates endoplasmic reticulum stress response elements and reverses acquired gefitinib resistance in HCC827 lung adenocarcinoma cells
    Authors: Liao, CH;Tzeng, YT;Lai, GM;Chang, CL;Hu, MH;Tsai, WL;Liu, YR;Hsia, S;Chuang, SE;Chiou, TJ;Wang, LM;Whang-Peng, J;Yao, CJ
    Contributors: National Institute of Cancer Research
    Abstract: Non-small cell lung cancer (NSCLC)-carrying specific epidermal growth factor receptor (EGFR) mutations can be effectively treated by a tyrosine kinase inhibitor such as gefitinib. However, the inevitable development of acquired resistance leads to the eventual failure of therapy. In this study, we show the combination effect of omega-3 fatty acid-enriched fish oil (FO) and selenium (Se) on reversing the acquired gefitinib-resistance of HCC827 NSCLC cells. The gefitinib-resistant subline HCC827GR possesses lowered proapoptotic CHOP (CCAAT/enhancer-binding protein homologous protein) and elevated cytoprotective GRP78 (glucose regulated protein of a 78 kDa molecular weight) endoplasmic reticulum (ER) stress response elements, and it has elevated β-catenin and cyclooxygenase-2 (COX-2) levels. Combining FO and Se counteracts the above features of HCC827GR cells, accompanied by the suppression of their raised epithelial-to-mesenchymal transition (EMT) and cancer stem markers, such as vimentin, AXL, N-cadherin, CD133, CD44, and ABCG2. Accordingly, an FO and Se combination augments the gefitinib-mediated growth inhibition and apoptosis of HCC827GR cells, along with the enhanced activation of caspase -3, -9, and ER stress-related caspase-4. Intriguingly, gefitinib further increases the elevated ABCG2 and cancer stem-like side population in HCC827GR cells, which can also be diminished by the FO and Se combination. The results suggest the potential of combining FO and Se in relieving the acquired resistance of NSCLC patients to targeted therapy.
    Date: 2020-07-29
    Relation: Marine Drugs. 2020 Jul 29;18(8):Article number 399.
    Link to: http://dx.doi.org/10.3390/md18080399
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1660-3397&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000564145100001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85089132314
    Appears in Collections:[Shuang-En Chuang] Periodical Articles

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