Antitumor effects of an adenovirus expressing antisense insulin-like growth factor I receptor on human lung cancer cell lines.

Abstract

Insulin-like growth factors (IGFs) are often essential for the maintenance of the malignant phenotype, and in lung cancer the IGF-I receptor (IGF-Ir) is often expressed at high levels. Stable transfection of antisense plasmids expressing the first 300 bp of the IGF-Ir reduces the tumorigenicity of a variety of tumor cell lines and has been reported to induce systemic antitumor effects on established, non-gene-modified tumors in animal model systems. We have constructed an adenovirus expressing an antisense IGF-Ir (Ad-IGF-Ir/as) in an attempt to develop these observations into a clinical therapeutic approach. A single transduction by Ad-IGF-Ir/as (at a multiplicity of infection of 10:1) decreased the IGF-Ir number by about 50% in human lung cancer cell lines NCI H460 and SCC5, as measured by an 125I-labeled IGF-I competitive binding assay. After the transduction of these human lung cancer cell lines by Ad-IGF-Ir/as, the soft agar clonogenicity was reduced by 84%. The i.p. treatment of nude mice bearing established i.p. NCI H460 cells resulted in prolonged survival compared to that of nude mice treated with a reporter virus. These results suggest that Ad-IGF-Ir/as has a therapeutic effect on established human lung cancer xenografts and may represent an effective and practical cancer gene therapy strategy.

• Authors: C T Lee, S Wu, D Gabrilovich, H Chen, S Nadaf-Rahrov, I F Ciernik, D P Carbone
• Journal: Cancer research (Cancer Res) Vol. 56 Issue 13 Pg. 3038-41 (Jul 01 1996) ISSN: 0008-5472 [Print] United States
• PMID: 8674059 (Publication Type: Journal Article)

Chemical References

• Iodine Radioisotopes
• Oligonucleotides, Antisense
• Insulin-Like Growth Factor I
• Agar
• Receptor, IGF Type 1

Topics

• Adenoviridae (genetics, metabolism)
• Agar
• Animals
• Base Sequence
• Binding, Competitive
• Carcinoma, Small Cell (genetics, therapy, ultrastructure)
• Cell Division (drug effects)
• Clone Cells
• Female
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Iodine Radioisotopes
• Lung Neoplasms (genetics, therapy, ultrastructure)
• Mice
• Mice, Nude
• Molecular Sequence Data
• Neoplasm Transplantation
• Oligonucleotides, Antisense (genetics, metabolism, pharmacology)
• Receptor, IGF Type 1 (biosynthesis, genetics, metabolism)
• Transduction, Genetic
• Transfection
• Transplantation, Heterologous
• Tumor Cells, Cultured