@article{aeaa246225b4453093a49820feeee85a,
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",
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.",
keywords = "acquired resistance, fish oil, gefitinib, lung cancer, selenium",
author = "Liao, {Chien Huang} and Tzeng, {Yu Tien} and Lai, {Gi Ming} and Chang, {Chia Lun} and Hu, {Ming Hung} and Tsai, {Wei Lun} and Liu, {Yun Ru} and Simon Hsia and Chuang, {Shuang En} and Chiou, {Tzeon Jye} and Wang, {Le Ming} and Jacqueline Whang-Peng and Yao, {Chih Jung}",
note = "Funding Information: Funding: This research was supported by the joint grant of Wan Fang Hospital, Taipei Medical University and New Health Products Co., Ltd., Taipei, Taiwan (Grant W327-2), Health and welfare surcharge of tobacco products Funding: This research was supported by the joint grant of Wan Fang Hospital, Taipei Medical University and (MOHW109-TDU-B-212-134020) and Ministry of Science and Technology, Taiwan (MOST 107-2314-B-038-080-MY2). New Health Products Co., Ltd., Taipei, Taiwan (Grant W327-2), Health and welfare surcharge of tobacco products (MOHW109-TDU-B-212-134020) and Ministry of Science and Technology, Taiwan (MOST Acknowledgments: The authors would like to thank Chih-Hung Guo (Institute of Biomedical Nutrition, 107-2314-B-038-080-MY2). The APC was funded by New Health Products Co., Ltd., Taipei, Taiwan. Hung-Kuang University, Taichung, Taiwan) for providing the selenium yeast and fish oil, and thank Yu-Ting Chou Acknowledgments: The authors would like to thank Chih-Hung Guo (Institute of Biomedical Nutrition, CHonufnligc-tKsuoafnIngtUerneisvte: rTshitiys,wToarickhwunasg,pTaartiiwalalyn)s ufoprpporrotevdidbinygthtehejo sinetlegnriaunmt oyfeWasatnaFnadnfgisHhosipl,itanl,dTtahipaenikMYeud-iTcianlg Chou (Institute of Biotechnology, National Tsing Hua University, Taiwan) for providing the HCC827GR cell Lai are the Principle Investigator and Co-Principle Investigator of the Grant W327-2, respectively. The funder line. participates in the scientific discussion of this work.",
year = "2020",
month = jul,
day = "29",
doi = "10.3390/md18080399",
language = "English",
volume = "18",
journal = "Marine Drugs",
issn = "1660-3397",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",
}