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: Xiao-Guang Lv, Meng-Yao Ji, Wei-Guo Dong, Xiao-Fei Lei, Meng Liu, Xu-Feng Guo, Jing Wang, Chuo Fang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 5 Issue 5 Pg. 1220-6 (May 2012) ISSN: 1791-3004 [Electronic] Greece
• PMID: 22366766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Phosphoproteins
• Sodium-Hydrogen Exchangers
• bcl-2-Associated X Protein
• sodium-hydrogen exchanger regulatory factor
• Fluorouracil

Topics

• Antimetabolites, Antineoplastic (pharmacology)
• Apoptosis (drug effects, genetics)
• Cell Line, Tumor
• Drug Resistance, Neoplasm (drug effects, genetics)
• Fluorouracil (pharmacology)
• Humans
• Mitochondria (genetics, metabolism, pathology)
• Phosphoproteins (biosynthesis, genetics)
• Sodium-Hydrogen Exchangers (biosynthesis, genetics)
• Stomach Neoplasms (genetics, metabolism, therapy)
• Transfection
• bcl-2-Associated X Protein (biosynthesis, genetics)