title: Overcoming 5-Fu resistance of colon cells through inhibition of Glut1 by the specific inhibitor WZB117.
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.
  
  
  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.
authors.affiliation: Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing, China E-mail : Liuwei140327@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Wang
authors.forename: Ju
authors.initials: J
authors.lastname: Liu
authors.forename: Xing
authors.initials: X
authors.lastname: Dan
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Sun
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D051272:Glucose Transporter Type 1; D062385:Hydroxybenzoates; C495677:SLC2A1 protein, human; C576807:WZB117; D005472:Fluorouracil