Inhibition of the EGFR with nanoparticles encapsulating antisense oligonucleotides of the EGFR enhances radiosensitivity in SCCVII cells

Abstract

The aim of this study is to evaluate the effects of antisense epidermal growth factor receptor (EGFR) nanoparticles on cell survival and radiosensitivity in the head and neck squamous cell carcinoma cell line SCCVII. Experiments were performed using the murine head-and-neck tumor cell line, SCCVII. Nanoparticle encapsulated antisense EGFR oligonucleotides were combined with radiotherapy and the relative radiosensitivity of the cells was assessed in vitro by MTT and standard colony formation. The proportion of apoptotic cells and cell cycle stages were analyzed by flow cytometry. C3H/He mice with SCCVII tumor heterografts were treated with antisense-EGFR-nanoparticles or RT alone, or with combinations of concomitant and sequential therapy. The relative radiosensitivity of the tumors was assessed in vivo by growth delay assays. The SCCVII cells were resistant to anti-EGFR nanoparticles or radiation therapy alone, but a synergic inhibition effect was observed when the therapies were combined. When the SCCVII cells were pre-treated with 2 mug of antisense-EGFR nanoparticles for 24 h and X-irradiated (4 Gy), flow cytometry analysis revealed cell cycle arrest in G(1) phase and an increased proportion of apoptotic cells. Our results show that antisense EGFR nanoparticles enhance radiosensitivity by inhibition of EGFR-mediated mechanisms of radioresistance. Collectively, these findings may have therapeutic implications because EGFR inhibition may improve the therapeutic efficacy of radiation even in the tumor cells that are resistant to anti-EGFR therapy.