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Differential effects of 5-fluorouracil on glucose transport and expressions of glucose transporter proteins in gastric cancer cells

Authors
Won, Hye-JinHa, Tae KyungKwon, Sung JoonCho, Hong YonHur, Sook-JinBaik, Hyung-HwanSuh, Seong-IlHa, EunyoungKim, Yong Ho
Issue Date
3월-2010
Publisher
LIPPINCOTT WILLIAMS & WILKINS
Keywords
5-fluorouracil; gastric cancer; glucose transport
Citation
ANTI-CANCER DRUGS, v.21, no.3, pp.270 - 276
Indexed
SCIE
SCOPUS
Journal Title
ANTI-CANCER DRUGS
Volume
21
Number
3
Start Page
270
End Page
276
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/116895
DOI
10.1097/CAD.0b013e328334562c
ISSN
0959-4973
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. Anti-Cancer Drugs 21: 270-276 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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