[The Roles of Glut5 in Imatinib Resistance in the Ph+ Acute Lymphoblastic Leukemia Cell]

Sichuan Da Xue Xue Bao Yi Xue Ban. 2017 May;48(3):389-393.
[Article in Chinese]

Abstract

Objectives: To explore the possible roles of glucose transport 5 (Glut5) in imatinib resistance in the Ph+ acute lymphoblastic leukemia cell (Ph+ ALL).

Methods: The gene chip technique was used to detect different gene expression between Ph+ ALL cell line SUP-B15/R (imatinib resistant cell line) and SUP-B15/S (imatinib sensitive cell line), the gene of solute carrier family 2 member 5 (SLC2A5) and its coded protein Glut5 were screened out and were reconfirmed by qPCR and Western blot assay. The imatinib half maximal inhibitory concentration (IC50) to SUP-B15/S cells with or without fructose treatment was further detected by MTT assay, simultaneously signal pathway gene was detected by qPCR assay.

Results: Metabolism related gene SLC2A5 was screened out with gene chip technique and the Western blot assay and qPCR confirmed the high expression of SLC2A5 gene and its coded protein Glut5 in SUP-B15/R cells. IC50 values of imatinib to SUP-B15/S cells after treatment with 25 μmol/L fructose were increased from (44.50±2.38) μmol/L to (64.71±1.69) μmol/L, in the meanwhile, PI3K and AKT mRNA level also increased in fructose treated SUP-B15/S cells compared to the control.

Conclusions: High expression of SLC2A5 and Glut5 protein in SUP-B15/R cells leads to increased fructose absorption, and further activates PI3K/AKT pathway which cause the SUP-B15 cell resistance to imatinib.

Keywords: Fructose; Glucose transport 5; Imatinib resistance; Ph+ acute lymphoblastic leukemia.

MeSH terms

  • Cell Line, Tumor
  • Drug Resistance, Neoplasm*
  • Glucose Transporter Type 5 / metabolism*
  • Humans
  • Imatinib Mesylate / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Glucose Transporter Type 5
  • SLC2A5 protein, human
  • Imatinib Mesylate
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt