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

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