GROWTH-INHIBITORY EFFECT OF ANTI-K-RAS ADENOVIRUS ON LUNG-CANCER CELLS

An adenoviral vector carrying a 2-Kb fragment of the K-ras proto-oncog ene inserted in antisense orientation with respect to the cytomegalovi rus promoter was constructed and used to infect H460a lung cancer cell s (codon 61 K-ras mutation). The gene was efficiently transferred, and a high level of expression of antisense K-ras was achieved. At a mult iplicity of infection to achieve 65% transduction of cells, the expres sion of K-ras protein was reduced by 70% in the lung cancer cell line H460a as compared with cells infected with control vectors or noninfec ted cells. This reduction produced a 47% inhibition of monolayer growt h and a 90% inhibition of colony formation. At a similar level of tran sduction in the cell line H358 (codon 12 K-ras mutation), a 59% inhibi tion of monolayer growth compared with control vectors occurred; howev er the inhibition of H322 cells (wild-type k-ras) growth was no differ ent than control vector infected cells. These data suggest that the ad enoviral K-ras H322a antisense vector may have therapeutic potential i n tumors in which K-ras is mutated.