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Effect on Cancer Cells of Plasmids That Express Antisense RNA of Human Papillomavirus Type 18

Department of Microbiology, University of Texas Dental Branch, Houston, Texas 77225 [C. S., K. A. S., E. J. S.], and Head and Neck Surgery Service, Memorial Sloan Kettering Cancer Center, New York, New York 10021 [P. G. S.]

Some human squamous cell carcinomas contain DNA of human papillomaviruses (HPV) and express RNA from the E6 and E7 genes. We have examined the effect of plasmids that express antisense RNA of these genes on the growth of the human cancer cell lines HeLa, C4-1, and 1483, which contain HPV type 18 DNA. As controls, the human cancer cell line 183 and the Vero line of monkey kidney cells were used, which do not contain HPV. Plasmids were introduced into the cells by electroporation; cells that contained HPV type 18 accepted the anti-sense-expressing plasmids at a lower frequency than the cells that lacked HPV. Cell lines were developed from HeLa cells that contained sense- or antisense-expressing plasmids, and lines that contained anti-sense-expressing plasmids showed slower growth, reduced ability to form colonies in soft agar, and increased serum requirements. The use of antisense HPV RNA might be a suitable approach to gene therapy of HPV-expressing human cancers.

Received 2/27/92. Accepted 6/22/92.

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