title: Differential effects of 5-fluorouracil on glucose transport and expressions of glucose transporter proteins in gastric cancer cells.
abstract: Although 5-fluorouracil (5-FU) is a widely used chemotherapeutic agent in the treatment of gastric cancer, the underlying mechanism for 5-FU resistant phenotype, has yet to be elucidated. We hypothesized that the sensitivity of gastric cancer to 5-FU treatment might be related to the rate of glucose transport (GLUT), and investigated the expressions of GLUT1, 2, 3, and 4 in two different gastric cancer cells (SNU-216, moderately differentiated gastric adenocarcinoma; and SNU-668, signet ring cell gastric carcinoma). Immunohistochemistry of GLUT1 and GLUT4 and immunoblot analysis of glycogen synthase kinase 3 were also performed. Hexokinase activity was measured. We found that 5-FU suppressed glucose uptake in SNU-216, while it stimulated GLUT in SNU-668. Further analysis revealed that 5-FU decreased the expression levels of GLUT1, 2, and 4 in SNU-216 cells and increased the expression levels of GLUT1, 2, and 4 in SNU-668 cells. Consistent with GLUT expression levels, immunohistochemistry analysis showed that 5-FU increased GLUT1 and GLUT4 levels in SNU-216 and decreased GLUT1 and GLUT4 levels in SNU-668. We also observed that glycogen synthase kinase 3 activity was decreased in SNU-216 and increased in SNU-668 with 5-FU treatment. No significant difference in hexokinase activities was observed with 5-FU treatment. Taken together, these results suggest that 5-FU exerts differential effects on GLUT depending on gastric cancer cell types, which may indicate a possible explanation, at least in part, for the differing responses to 5-FU chemotherapy in gastric cancer.
authors.affiliation: Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Won
authors.forename: Tae Kyung
authors.initials: TK
authors.lastname: Ha
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kwon
authors.forename: Hong Yon
authors.initials: HY
authors.lastname: Cho
authors.forename: Sook-Jin
authors.initials: SJ
authors.lastname: Hur
authors.forename: Hyung-Hwan
authors.initials: HH
authors.lastname: Baik
authors.forename: Seong-Il
authors.initials: SI
authors.lastname: Suh
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Ha
authors.forename: Yong Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D018279:Carcinoma, Signet Ring Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D005472:Fluorouracil / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D013274:Stomach Neoplasms / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D051246:Glucose Transport Proteins, Facilitative; D006593:Hexokinase; D038362:Glycogen Synthase Kinase 3; D005947:Glucose; D005472:Fluorouracil