Targeted Inhibition of the EGFR Pathways Enhances Zn-BC-AM PDT-Induced Apoptosis in Well-Differentiated Nasopharyngeal Carcinoma Cells

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 AG 1478 were investigated. Well-differentiated NPC HK-1 cells were subjected to PDT with 1 mu M of Zn-BC-AM and were irradiated at a light dose of 1 J/cm(2) in the presence or absence of EGFR inhibitor AG 1478. 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 AG 1478. A sub-lethal concentration of AG 1478 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 (AG 1478), 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. J. Cell. Biochem. 108: 13561363, 2009. (C) 2009 Wiley-Liss, Inc