TY - JOUR
T1 - Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter
AU - He, Yukai
AU - Zeng, Qing
AU - Drenning, Stephanie D.
AU - Melhem, Mona F.
AU - Tweardy, David J.
AU - Huang, Leaf
AU - Grandis, Jennifer Rubin
N1 - Funding Information:
Supported in part by the John R. McCune Charitable Trust Foundation; by the Mary Hillman Jennings Foundation; by The Eye & Ear Foundation; by grant #0681-01 from The Smokeless Tobacco Research Council; and by Public Health Service grants CA64654, CA71730 (L. Huang), CA01760, and CA72526 [J. R. Grandis) from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.
PY - 1998/7/15
Y1 - 1998/7/15
N2 - Background: Squamous cell carcinomas of the head and neck (SCCHN), unlike normal mucosal squamous epithelial cells, overexpress epidermal growth factor receptor (EGFR) messenger RNA and protein. EGFR protein is required to sustain the proliferation of SCCHN cells in vitro. To determine whether EGFR expression contributes to tumor growth, we investigated the effect of suppressing EGFR expression in tumor xenografts through in situ expression of antisense oligonucleotides. Methods: Intratumoral cationic liposome-mediated gene transfer was used to deliver plasmids capable of expressing sense or antisense EGFR sequences into human head and neck tumors, which were grown as subcutaneous xenografts in nude mice. The oligonucleotides were expressed under the control of the U6 RNA promoter. Results: Direct inoculation of the EGFR antisense (but not the corresponding sense) plasmid construct into established SCCHN xenografts resulted in inhibition of tumor growth, suppression of EGFR protein expression, and an increased rate of apoptosis (programmed cell death). Sustained antitumor effects were observed for up to 2 weeks after the treatments were discontinued. Conclusion: These results suggest that interference with EGFR expression, using an antisense-based gene therapy approach, may be an effective means of treating EGFR-overexpressing tumors, including SCCHN.
AB - Background: Squamous cell carcinomas of the head and neck (SCCHN), unlike normal mucosal squamous epithelial cells, overexpress epidermal growth factor receptor (EGFR) messenger RNA and protein. EGFR protein is required to sustain the proliferation of SCCHN cells in vitro. To determine whether EGFR expression contributes to tumor growth, we investigated the effect of suppressing EGFR expression in tumor xenografts through in situ expression of antisense oligonucleotides. Methods: Intratumoral cationic liposome-mediated gene transfer was used to deliver plasmids capable of expressing sense or antisense EGFR sequences into human head and neck tumors, which were grown as subcutaneous xenografts in nude mice. The oligonucleotides were expressed under the control of the U6 RNA promoter. Results: Direct inoculation of the EGFR antisense (but not the corresponding sense) plasmid construct into established SCCHN xenografts resulted in inhibition of tumor growth, suppression of EGFR protein expression, and an increased rate of apoptosis (programmed cell death). Sustained antitumor effects were observed for up to 2 weeks after the treatments were discontinued. Conclusion: These results suggest that interference with EGFR expression, using an antisense-based gene therapy approach, may be an effective means of treating EGFR-overexpressing tumors, including SCCHN.
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U2 - 10.1093/jnci/90.14.1080
DO - 10.1093/jnci/90.14.1080
M3 - Article
C2 - 9672256
AN - SCOPUS:0032528051
SN - 0027-8874
VL - 90
SP - 1080
EP - 1087
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 14
ER -