Tumour Therapy with Genes Encoding Apoptin and E4orf4

The aim of our study was to investigate whether apoptin and e4orf4 pro-apoptotic genes, transferred by means of electroporation, were suitable for gene therapy of tumours. The two genes were chosen for our study because the proteins they encode induce apoptosis in transformed cells only. The apoptin gene was synthesised based on a published nucleotide sequence. MTT and TUNEL tests confirmed that both the synthesised apoptin gene and the e4orf4 gene indeed induced apoptosis in COS-7, Renca and B16(F10) cell lines. Therapeutic DNA was then administered via electroporation directly into murine B16(F10) tumours. Distinct tumour growth inhibition was seen only during the treatment. The cessation of therapy caused tumour re-growth. Obviously, the efficiency of gene transfer using electroporation is low and did not induce a permanent therapeutic effect. The pro-apoptotic genes, apoptin and e4orf4, are of viral origin (1-4). They were used in the study because the proteins they encode induce apoptosis in transformed cells, but not in normal cells.