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BioMed Research International
Volume 2013 (2013), Article ID 293874, 10 pages
http://dx.doi.org/10.1155/2013/293874
Research Article

The Synergistic Effects of Low Dose Fluorouracil and TRAIL on TRAIL-Resistant Human Gastric Adenocarcinoma AGS Cells

1Department of Abdominal Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
2Department of Pathophysiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China
3Department of Nuclear Medicine, Tai’an Central Hospital, Tai’an, Shandong 271000, China

Received 20 May 2013; Accepted 30 September 2013

Academic Editor: Thomas Griffith

Copyright © 2013 Hong Zhu et al. 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.

Abstract

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.