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Overcoming 5-Fu Resistance of Colon Cells through Inhibition of Glut1 by the Specific Inhibitor WZB117

  • Liu, Wei (Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University) ;
  • Fang, Yong (Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University) ;
  • Wang, Xiao-Tong (Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University) ;
  • Liu, Ju (Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University) ;
  • Dan, Xing (Northeast Pharmaceutical Group Sales Co., Ltd.) ;
  • Sun, Lu-Lu (Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University)
  • Published : 2014.09.15

Abstract

Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers.

Keywords

5-Fluorouracil;colon cancer;glut1;specific inhibitor;WZB117

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