title: Contribution of Epstein-Barr virus infection to chemoresistance of gastric carcinoma cells to 5-fluorouracil.
abstract: Although Epstein-Barr virus (EBV) is associated with 6-16% of the gastric carcinoma (GC) cases, the effect of EBV infection on the tumorigenesis process and the responsiveness to chemotherapy remain unclear. We compared chemosensitivity of the EBV-positive GC (AGSEBV) and EBV-negative GC (AGS) cells to 5-fluorouracil (5-FU). Although 5-FU inhibited the growth of both cell lines in a dose- and time-dependent manner, the sensitivity of EBV-positive GC cells to 5-FU was lower than that of EBV-negative GC cells. The cleavage of PARP and caspase-3 was also lower in AGS-EBV cells than in AGS cells following 5-FU treatment. Both the level of Bcl-2 expression and the ratio of Bcl-2/Bax were higher in AGS-EBV than in AGS cells not only at basal state but also following 5-FU treatment. Moreover, p53 and p21 expression was enhanced further by 5-FU in AGS than in AGS-EBV cells. Immunofluorescence assay and Western blot showed that 5-FU induced the expression of EBV-lytic genes including BZLF1, BRLF1, BMRF1 and BHRF1. Our results suggest that latent and lytic EBV infection contributes to the chemoresistance to 5-FU in gastric carcinoma by modulating apoptosis related cellular genes.
authors.affiliation: Research Institute of Immunobiology, Department of Medical Lifescience, College of Medicine, Catholic University of Korea, Seoul, 137-701, Korea.
authors.forename: Jung Seon
authors.initials: JS
authors.lastname: Seo
authors.forename: Tai-Gyu
authors.initials: TG
authors.lastname: Kim
authors.forename: Young Seon
authors.initials: YS
authors.lastname: Hong
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Chen
authors.forename: Suk Kyeong
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D020031:Epstein-Barr Virus Infections / Q000378:metabolism / Q000473:pathology*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D009363:Neoplasm Proteins; D005472:Fluorouracil