Department of Biology
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 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.
EGFR, NPC, Photodynamic therapy
Source Publication Title
Journal of Cellular Biochemistry
Link to Publisher's Edition
Koon, Ho-Kee, Pui-Shan Chan, Ricky Ngok-Shun Wong, Zhen-Guo Wu, Maria Li Lung, Chi-Kwong Chang, and Nai-Ki Mak. "Targeted inhibition of the EGFR pathways enhances Zn-BC-AM PDT-induced apoptosis in well-differentiated nasopharyngeal carcinoma cells." Journal of Cellular Biochemistry 108.6 (2009): 1356-1363.