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

被引：18

作者：

Liao, Chien-Huang ^{[1
]}

Tzeng, Yu-Tien ^{[2
]}

Lai, Gi-Ming ^{[1
,3
]}

Chang, Chia-Lun ^{[3
,4
]}

Hu, Ming-Hung ^{[3
]}

Tsai, Wei-Lun ^{[1
]}

Liu, Yun-Ru ^{[5
]}

Hsia, Simon ^{[6
]}

Chuang, Shuang-En ^{[7
]}

Chiou, Tzeon-Jye ^{[1
]}

Wang, Le-Ming ^{[8
]}

Whang-Peng, Jacqueline ^{[1
]}

Yao, Chih-Jung ^{[1
,4
]}

机构：

[1] Taipei Med Univ, Wan Fang Hosp, Canc Ctr, Taipei 11696, Taiwan

[2] Taipei Med Univ, Wan Fang Hosp, Div Pulm Med, Taipei 11696, Taiwan

[3] Taipei Med Univ, Wan Fang Hosp, Dept Internal Med, Div Hematol & Med Oncol, Taipei 11696, Taiwan

[4] Taipei Med Univ, Coll Med, Sch Med, Dept Internal Med, Taipei 11031, Taiwan

[5] Taipei Med Univ, Off Human Res, Joint Biobank, Taipei 11031, Taiwan

[6] Taiwan Nutraceut Assoc, Taipei 10596, Taiwan

[7] Natl Hlth Res Inst, Natl Inst Canc Res, Miaoli 35053, Taiwan

[8] Taipei Med Univ, Wan Fang Hosp, Dept Obstet & Gynecol, Taipei 11696, Taiwan

来源：

MARINE DRUGS | 2020年 / 18卷 / 08期

关键词：

lung cancer; fish oil; selenium; gefitinib; acquired resistance; CANCER CELLS; ER STRESS; GRP78; EXPRESSION; ACTIVATION; APOPTOSIS; SUPPLEMENTATION; PHOTOSYNTHESIS; INHIBITION; MUTATIONS;

D O I：

10.3390/md18080399

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 beta-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.

引用

页数：16