title: The synergistic effects of low dose fluorouracil and TRAIL on TRAIL-resistant human gastric adenocarcinoma AGS cells.
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.
authors: Department of Abdominal Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors: Hong
authors: H
authors: Zhu
authors: Min
authors: M
authors: Huang
authors: Daoling
authors: D
authors: Ren
authors: Jianping
authors: J
authors: He
authors: Fen
authors: F
authors: Zhao
authors: Cheng
authors: C
authors: Yi
authors: Ying
authors: Y
authors: Huang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage*; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D012235:Rhodamines / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage* / Q000378:metabolism; D053319:Tumor Necrosis Factor Decoy Receptors / Q000096:biosynthesis
chemical_list: D058851:GPI-Linked Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D012235:Rhodamines; D053221:TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; C108661:TNFRSF10C protein, human; C505653:TNFSF10 protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; C022027:lissamine rhodamine B; D005472:Fluorouracil