Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter

Yukai He, Qing Zeng, Stephanie D. Drenning, Mona F. Melhem, David J. Tweardy, Leaf Huang, Jennifer Rubin Grandis

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1080-1087
Number of pages8
JournalJournal of the National Cancer Institute
Volume90
Issue number14
DOIs
StatePublished - Jul 15 1998
Externally publishedYes

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Antisense RNA
Epidermal Growth Factor Receptor
Squamous Cell Carcinoma
Growth
Heterografts
Neoplasms
Plasmids
Proteins
Antisense Oligonucleotides
Nude Mice
Liposomes
Oligonucleotides
Genetic Therapy
Cell Death
Neck
Epithelial Cells
Head
Apoptosis
Messenger RNA
Carcinoma, squamous cell of head and neck

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter. / He, Yukai; Zeng, Qing; Drenning, Stephanie D.; Melhem, Mona F.; Tweardy, David J.; Huang, Leaf; Grandis, Jennifer Rubin.

In: Journal of the National Cancer Institute, Vol. 90, No. 14, 15.07.1998, p. 1080-1087.

Research output: Contribution to journalArticle

He, Yukai ; Zeng, Qing ; Drenning, Stephanie D. ; Melhem, Mona F. ; Tweardy, David J. ; Huang, Leaf ; Grandis, Jennifer Rubin. / Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter. In: Journal of the National Cancer Institute. 1998 ; Vol. 90, No. 14. pp. 1080-1087.
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