Document Type

Journal Article

Department/Unit

Department of Biology

Title

Targeted inhibition of the EGFR pathways enhances Zn-BC-AM PDT-induced apoptosis in well-differentiated nasopharyngeal carcinoma cells

Language

English

Abstract

Epidermal growth factor receptor (EGFR), a receptor often expressed in nasopharyngeal carcinoma (NPC) cells, is one of the recently identified molecular targets in cancer treatment. In the present study, the effects of combined treatment of Zn-BC-AM PDT with an EGFR inhibitor AG1478 were investigated. Well-differentiated NPC HK-1 cells were subjected to PDT with 1 μM of Zn-BC-AM and were irradiated at a light dose of 1 J/cm2 in the presence or absence of EGFR inhibitor AG1478. Specific protein kinase inhibitors of downstream EGFR targets were also used in the investigation. EGFR, Akt, and ERK were found constitutively activated in HK-1 cells and the activities could be inhibited by the EGFR inhibitor AG1478. A sub-lethal concentration of AG1478 was found to further enhance the irreversible cell damage induced by Zn-BC-AM PDT in HK-1 cells. Pre-incubation of the cells with specific inhibitors of EGFR (AG1478), PI3k/Akt (LY294002), or MEK/ERK (PD98059) before light irradiation were found to enhance Zn-BC-AM PDT-induced formation of apoptotic cells. The efficacy of Zn-BC-AM PDT can be increased through the inhibition of EGFR/PI3K/Akt and EGFR/MEK/ERK signaling pathways in NPC cells. Combination therapy with Zn-BC-AM PDT and EGFR inhibitors may further be developed for the treatment of advanced NPC. © 2009 Wiley-Liss, Inc.

Keywords

EGFR, NPC, Photodynamic therapy

Publication Date

2009

Source Publication Title

Journal of Cellular Biochemistry

Volume

108

Issue

6

Start Page

1356

End Page

1363

Publisher

Wiley

DOI

10.1002/jcb.22366

Link to Publisher's Edition

http://dx.doi.org/10.1002/jcb.22366

ISSN (print)

07302312

ISSN (electronic)

10974644

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