INHIBITION OF HUMAN SQUAMOUS-CELL CARCINOMA GROWTH IN-VIVO BY EPIDERMAL GROWTH-FACTOR RECEPTOR ANTISENSE RNA TRANSCRIBED FROM THE U6 PROMOTER

Background: Squamous cell carcinomas of the head and neck (SCCHN), unl ike normal mucosal squamous epithelial cells, overexpress epidermal gr owth factor receptor (EGFR) messenger RNA and protein, EGFR protein is required to sustain the proliferation of SCCHN cells in vitro. To det ermine whether EGFR expression contributes to tumor growth, me investi gated the effect of suppressing EGFR expression in tumor xenografts th rough in situ expression of antisense oligonucleotides, Methods: Intra tumoral cationic liposome-mediated gene transfer was used to deliver p lasmids capable of expressing sense or antisense EGFR sequences into h uman head and neck tumors, which were grown as subcutaneous xenografts in nude mice. The oligonucleotides were expressed under the control o f the U6 RNA promoter. Results: Direct inoculation of the EGFR antisen se (but not the corresponding sense) plasmid construct into establishe d SCCHN xenografts resulted in inhibition of tumor growth, suppression of EGFR protein expression, and an increased rate of apoptosis (progr ammed cell death). Sustained antitumor effects were observed for up to 2 weeks after the treatments mere discontinued, Conclusion: These res ults suggest that interference with EGFR expression, using an antisens e-based gene therapy approach, may be an effective means of treating E GFR-overexpressing tumors, including SCCHN.