Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Hong, Huang, Min, Ren, Daoling, He, Jianping, Zhao, Fen, Yi, Cheng, Huang, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
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
_version_ 1782293371399700480
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
work_keys_str_mv AT zhuhong thesynergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT huangmin thesynergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT rendaoling thesynergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT hejianping thesynergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT zhaofen thesynergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT yicheng thesynergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT huangying thesynergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT zhuhong synergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT huangmin synergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT rendaoling synergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT hejianping synergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT zhaofen synergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT yicheng synergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells
AT huangying synergisticeffectsoflowdosefluorouracilandtrailontrailresistanthumangastricadenocarcinomaagscells