当前位置： SCI文献检索 > CANCER CHEMOTHERAPY AND PHARMACOLOGY期刊下所有文献 > Significant increase in hEGF uptake is correlated with formation of EGFR dimers induced by the EGFR tyrosine kinase inhibitor gefitinib.

Significant increase in hEGF uptake is correlated with formation of EGFR dimers induced by the EGFR tyrosine kinase inhibitor gefitinib.

Abstract：

PURPOSE:The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib (ZD1839, Iressa) is approved for cancer treatment. We investigated whether gefitinib treatment can enhance human EGF (hEGF) uptake in vitro, thereby increasing the potential of hEGF as a vehicle for EGFR-targeted therapy. METHODS:Western blotting was used to detect the effect of gefitinib on EGFR signaling. Different EGFR-expressing tumor cells (SCC-1, 22B, A549, and HT-29) were pretreated with gefitinib, and then with (125)I-hEGF or (125)I-Vectibix (an anti-EGFR monoclonal antibody). Cell-associated activity was then measured. A cross-linking assay detected increased EGFR dimer formation in gefitinib-treated cells. RESULTS:Total EGFR levels were not changed, but EGFR phosphorylation was reduced in cells pretreated with gefitinib. Gefitinib mediated formation of EGFR dimers; binding of (125)I-hEGF to cells pretreated with gefitinib significantly increased. In contrast, binding of (125)I-Vectibix to tumor cells did not increase. Although total EGFR levels did not increase, binding of hEGF to EGFR + tumors was significantly enhanced after gefitinib treatment, because of increased hEGF binding to gefitinib-induced EGFR dimers. CONCLUSION:These results suggest that hEGF could enhance EGFR-targeting when used with gefitinib.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

He P,Li G

doi

10.1007/s00280-013-2198-6

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

341-8

issue

2

eissn

0344-5704

issn

1432-0843

journal_volume

72

pub_type

杂志文章

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