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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.
Liao, Chien-Huang; Tzeng, Yu-Tien; Lai, Gi-Ming; Chang, Chia-Lun; Hu, Ming-Hung; Tsai, Wei-Lun; Liu, Yun-Ru; Hsia, Simon; Chuang, Shuang-En; Chiou, Tzeon-Jye; Wang, Le-Ming; Whang-Peng, Jacqueline; Yao, Chih-Jung.
Afiliación
  • Liao CH; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
  • Tzeng YT; Division of Pulmonary Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
  • Lai GM; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
  • Chang CL; Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
  • Hu MH; Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
  • Tsai WL; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • Liu YR; Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
  • Hsia S; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
  • Chuang SE; Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 11031, Taiwan.
  • Chiou TJ; Taiwan Nutraceutical Association, Taipei 10596, Taiwan.
  • Wang LM; National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan.
  • Whang-Peng J; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
  • Yao CJ; Department of Obstetrics and Gynecology, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
Mar Drugs ; 18(8)2020 Jul 29.
Article en En | MEDLINE | ID: mdl-32751169
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 ß-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Selenio / Ácidos Grasos Omega-3 / Carcinoma de Pulmón de Células no Pequeñas / Resistencia a Antineoplásicos / Estrés del Retículo Endoplásmico / Gefitinib / Adenocarcinoma del Pulmón / Neoplasias Pulmonares / Antineoplásicos Límite: Humans Idioma: En Revista: Mar Drugs Asunto de la revista: BIOLOGIA / FARMACOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Selenio / Ácidos Grasos Omega-3 / Carcinoma de Pulmón de Células no Pequeñas / Resistencia a Antineoplásicos / Estrés del Retículo Endoplásmico / Gefitinib / Adenocarcinoma del Pulmón / Neoplasias Pulmonares / Antineoplásicos Límite: Humans Idioma: En Revista: Mar Drugs Asunto de la revista: BIOLOGIA / FARMACOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza