Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells by antisense RNA.

A human lung cancer cell line (H460a) with a homozygous spontaneous K-ras mutation was transfected with a recombinant plasmid that synthesizes a 2-kilobase genomic segment of the K-ras protooncogene in antisense orientation. Translation of the mutated K-ras mRNA in H460a cells was specifically inhibited, whereas expression of H-ras and N-ras was unchanged. A 3-fold growth inhibition occurred in H460a cells when expression of the mutated ras p21 protein was down-regulated by antisense RNA. However, cells remained viable despite the absence of K-ras expression. The growth of H460a tumors in nu/nu mice was substantially reduced by expressed K-ras antisense RNA.