Gefitinib inhibits sodium phosphate co-transporter III isoform 1 in a model of human malignant glioma

Anticancer Res. 2014 Nov;34(11):6527-35.

Abstract

Background: The purpose of the present was to investigate whether the in vitro effects of gefitinib, an EGFR tyrosine kinase inhibitor, may regulate the expression of type III sodium phosphate Na/Pi co-transporters in an in vitro glioma model.

Materials and methods: Proliferation studies, global native EGFR and phosphorylated EGFR expressions, phosphate transporter type III isoform 1(PiT1) expression and phosphate transport with 99mTc-(V)-DMSA radioligand were performed in G111 (grade II astrocytoma), U-87-MG (grade III astrocytoma) and G152 (grade IV glioblastoma) cells.

Results: Cells treated with gefitinib showed a significant decrease in proliferation in relation to EGFR and p-EGFR expression. Gefitinib also produced a decrease in phosphate transport mediated PIT1 expression at both the RNA and protein levels.

Conclusion: The link between gefitinib acting on the EGFR and PiT1 regulation in these cancer cell lines was herein shown.

Keywords: EGFR signaling; Gefitinib; PiT-1; malignant gliomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Gefitinib
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Neoplasm Grading
  • Phosphates / metabolism
  • Protein Isoforms
  • Quinazolines / pharmacology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium-Phosphate Cotransporter Proteins, Type III / antagonists & inhibitors*
  • Sodium-Phosphate Cotransporter Proteins, Type III / genetics
  • Sodium-Phosphate Cotransporter Proteins, Type III / metabolism
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Phosphates
  • Protein Isoforms
  • Quinazolines
  • RNA, Messenger
  • Sodium-Phosphate Cotransporter Proteins, Type III
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib