title: EBP50 gene transfection promotes 5-fluorouracil-induced apoptosis in             gastric cancer cells through Bax- and Bcl-2-triggered mitochondrial pathways.
abstract: 5-Fluorouracil (5-FU) plays an important role in the chemotherapy of advanced gastric cancer. However, genetic factors that affect therapeutic efficacy of 5-FU warrant further investigation. In the present study, using stable transfection of the ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) gene, we explored the genetic influences on 5-FU-induced apoptosis of human gastric cancer cells. Stable overexpression of the EBP50 gene was determined by reverse transcription polymerase chain reaction (RT-PCR) assay and western blot analysis. After treatment with 5-FU, cell growth activities in vitro were investigated by MTT assay. Cell apoptosis was evaluated by Hoechst 33258 staining and flow cytometry of Annexin V-FITC/PI staining. Compared with the BGC823 or BGC823/neo cells, EBP50 mRNA and protein levels in the BGC823/EBP50 cells (EBP50-transfected BGC823 cells) were markedly higher. Chemosensitivity and apoptosis rates of the BGC823/EBP50 cells were higher compared to the BGC823 and BGC823/neo cells following treatment with 5-FU. Stable overexpression of extrinsic EBP50 distinctly increases the 5-FU-induced apoptosis of gastric cancer cells, and is a novel strategy by which to improve the chemosensitivity of gastric cancer to 5-FU.
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Lv
authors.forename: Meng-Yao
authors.initials: MY
authors.lastname: Ji
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Dong
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Lei
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Guo
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Chuo
authors.initials: C
authors.lastname: Fang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D051028:bcl-2-Associated X Protein; C093376:sodium-hydrogen exchanger regulatory factor; D005472:Fluorouracil