Suppression of the malignant phenotype of melanoma cells by anti-oncogene ribozymes.

The activation of signal transduction pathways by mutation or overexpression of cellular oncogenes has been associated with neoplastic transformation. In this study, we addressed the therapeutic potential of ribozymes targeted against the activated H-ras oncogene as well as against the nuclear proto-oncogenes c-fos and c-myc in the FEM human melanoma cell line containing a H-ras mutation. FEM cells transfected with the anti-ras ribozyme were shown to have the longest doubling time, the least DNA synthesis, and the fewest colonies in soft agar when compared with transfectants with ribozymes against c-fos or c-myc mRNA. Furthermore, anti-ras ribozyme clones showed a dendritic appearance in monolayer culture that was associated with enhanced melanin synthesis. These results suggest that the anti-ras ribozyme could affect not only the proliferation but also the differentiation process of human melanoma cells in vitro. They also reinforce the role of anti-oncogene ribozymes as suppressors of the neoplastic phenotype of melanoma cells.