Abstract
An adenoviral vector carrying a 2-Kb fragment of the K-ras proto-oncogene inserted in antisense orientation with respect to the cytomegalovirus promoter was constructed and used to infect H460a lung cancer cells (codon 61 K-ras mutation). The gene was efficiently transferred, and a high level of expression of antisense K-ras was achieved. At a multiplicity of infection to achieve 65% transduction of cells, the expression of K-ras protein was reduced by 70% in the lung cancer cell line H460a as compared with cells infected with control vectors or noninfected cells. This reduction produced a 47% inhibition of monolayer growth and a 90% inhibition of colony formation. At a similar level of transduction in the cell line H358 (codon 12 K-ras mutation), a 59% inhibition of monolayer growth compared with control vectors occurred; however the inhibition of H322 cells (wild-type k-ras) growth was no different than control vector infected cells. These data suggest that the adenoviral K-ras H322a antisense vector may have therapeutic potential in tumors in which K-ras is mutated.
Original language | English (US) |
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Pages (from-to) | 296-301 |
Number of pages | 6 |
Journal | Cancer gene therapy |
Volume | 3 |
Issue number | 5 |
State | Published - 1996 |
Keywords
- Adenovirus
- Antisense
- Cancer
- K-ras
- Lung
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Cancer Research