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The Synergistic Effects of Low Dose Fluorouracil and TRAIL on TRAIL-Resistant Human Gastric Adenocarcinoma AGS Cells
The TNF-related apoptosis-inducing ligand (TRAIL) is a TNF family member which has been under intense focus because of its remarkable ability to induce apoptosis in malignant human cells while leaving normal cells unscathed. However, many cancer cells remain resistant to TRAIL. In this study, we had...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3845848/ https://www.ncbi.nlm.nih.gov/pubmed/24324958 http://dx.doi.org/10.1155/2013/293874 |
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author | Zhu, Hong Huang, Min Ren, Daoling He, Jianping Zhao, Fen Yi, Cheng Huang, Ying |
author_facet | Zhu, Hong Huang, Min Ren, Daoling He, Jianping Zhao, Fen Yi, Cheng Huang, Ying |
author_sort | Zhu, Hong |
collection | PubMed |
description | The TNF-related apoptosis-inducing ligand (TRAIL) is a TNF family member which has been under intense focus because of its remarkable ability to induce apoptosis in malignant human cells while leaving normal cells unscathed. However, many cancer cells remain resistant to TRAIL. In this study, we had investigated the synergistic effects of low dose fluorouracil (5-Fu) and TRAIL on TRAIL-resistant human gastric adenocarcinoma AGS cells and explored the potential mechanisms. Cell viability was analyzed by sulforhodamine B (SRB) assay and the synergistic effects were evaluated by Jin's formula and confirmed by both morphological changes under inverted microscope and flow cytometry. The expression of TRAIL-R1 (death receptor 4, DR4), TRAIL-R2 (DR5), TRAIL-R3 (decoy receptor, DcR1), TRAIL-R4 (DcR2), procaspase-3, procaspase-8, and procaspase-9 was detected by western blotting. Our results showed that there were significant synergistic effects of low dose 5-Fu and TRAIL on TRAIL-resistant AGS cells, and this effect was supposed to be mediated by decreasing DcR2 expression and increasing DR5 expression. The extrinsic and intrinsic apoptosis pathways were both activated. The data suggest that combined treatment of low dose 5-Fu and TRAIL can be an effective therapeutic approach for gastric adenocarcinoma. |
format | Online Article Text |
id | pubmed-3845848 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-38458482013-12-09 The Synergistic Effects of Low Dose Fluorouracil and TRAIL on TRAIL-Resistant Human Gastric Adenocarcinoma AGS Cells Zhu, Hong Huang, Min Ren, Daoling He, Jianping Zhao, Fen Yi, Cheng Huang, Ying Biomed Res Int Research Article The TNF-related apoptosis-inducing ligand (TRAIL) is a TNF family member which has been under intense focus because of its remarkable ability to induce apoptosis in malignant human cells while leaving normal cells unscathed. However, many cancer cells remain resistant to TRAIL. In this study, we had investigated the synergistic effects of low dose fluorouracil (5-Fu) and TRAIL on TRAIL-resistant human gastric adenocarcinoma AGS cells and explored the potential mechanisms. Cell viability was analyzed by sulforhodamine B (SRB) assay and the synergistic effects were evaluated by Jin's formula and confirmed by both morphological changes under inverted microscope and flow cytometry. The expression of TRAIL-R1 (death receptor 4, DR4), TRAIL-R2 (DR5), TRAIL-R3 (decoy receptor, DcR1), TRAIL-R4 (DcR2), procaspase-3, procaspase-8, and procaspase-9 was detected by western blotting. Our results showed that there were significant synergistic effects of low dose 5-Fu and TRAIL on TRAIL-resistant AGS cells, and this effect was supposed to be mediated by decreasing DcR2 expression and increasing DR5 expression. The extrinsic and intrinsic apoptosis pathways were both activated. The data suggest that combined treatment of low dose 5-Fu and TRAIL can be an effective therapeutic approach for gastric adenocarcinoma. Hindawi Publishing Corporation 2013 2013-11-13 /pmc/articles/PMC3845848/ /pubmed/24324958 http://dx.doi.org/10.1155/2013/293874 Text en Copyright © 2013 Hong Zhu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhu, Hong Huang, Min Ren, Daoling He, Jianping Zhao, Fen Yi, Cheng Huang, Ying The Synergistic Effects of Low Dose Fluorouracil and TRAIL on TRAIL-Resistant Human Gastric Adenocarcinoma AGS Cells |
title | The Synergistic Effects of Low Dose Fluorouracil and TRAIL on TRAIL-Resistant Human Gastric Adenocarcinoma AGS Cells |
title_full | The Synergistic Effects of Low Dose Fluorouracil and TRAIL on TRAIL-Resistant Human Gastric Adenocarcinoma AGS Cells |
title_fullStr | The Synergistic Effects of Low Dose Fluorouracil and TRAIL on TRAIL-Resistant Human Gastric Adenocarcinoma AGS Cells |
title_full_unstemmed | The Synergistic Effects of Low Dose Fluorouracil and TRAIL on TRAIL-Resistant Human Gastric Adenocarcinoma AGS Cells |
title_short | The Synergistic Effects of Low Dose Fluorouracil and TRAIL on TRAIL-Resistant Human Gastric Adenocarcinoma AGS Cells |
title_sort | synergistic effects of low dose fluorouracil and trail on trail-resistant human gastric adenocarcinoma ags cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3845848/ https://www.ncbi.nlm.nih.gov/pubmed/24324958 http://dx.doi.org/10.1155/2013/293874 |
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