Specific Growth Inhibition of Small‐cell Lung Cancer Cells by Adenovirus Vector Expressing Antisense c‐kit Transcripts

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Abstract
Antisense methods to control aberrant gene expression have been investigated as therapeutic strategies. A proto‐oncogene c‐kit, which encodes a transmembrane tyrosine kinase, is overexpressed in some malignancies, including small‐cell lung cancer (SCLC), and is thought to be involved in their pathogenesis. To test the feasibility of using adenovirus vectors for antisense strategies and to target c‐kit in SCLC therapy, we constructed replication‐deficient recombinant adenovirus vectors which express fragments of c‐kit transcripts in antisense (Ad.kitAS) or sense orientation (Ad.kitS: control). In vitro infection of SBC‐1 cells, which are c‐Kit protein‐producing SCLC cells, by these vectors resulted in the expression of artificial c‐kit transcripts. The Ad.kitAS‐infected SBC‐1 cells showed reductions in the amount of c‐Kit protein. As expected, at 10 days after infection (1 multiplicity of infection), Ad.kitAS‐infected SBC‐1 cells showed approximately 40% growth inhibition compared to uninfected or Ad.kitS‐infected cells in vitro. Such a significant growth inhibition by Ad.kitAS was not induced in SBC‐5 cells, which are SCLC cells producing no c‐Kit protein. These results demonstrate the usefulness of adenovirus vectors in antisense strategies, and the feasibility of targeting c‐kit in the therapy of c‐Kit‐producing SCLC.