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Specific Inhibition of K-ras Expression and Tumorigenicity of Lung Cancer Cells by Antisense RNA¹

Departments of Thoracic Surgery [T. M., A. C. C., J. A. R.] and Tumor Biology [M. T., J. A. R.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

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.

¹ This work was supported in part by NIH grants CA45187 [J.A.R.] and CA42810 [M.T.].

² To whom requests for reprints should be addressed, at The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard/Box 109, Houston, TX 77030.

Received 1/ 9/91. Accepted 1/31/91.

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