BACKGROUND: The expression of FasL in cancer cells is currently being explored as a potential cancer therapy. Because high levels of FasL are necessary for effective treatment, current methods typically rely on the use of highly efficient viral vectors. However, because viral vector-based gene therapy is associated with certain risks, the development of effective nonviral routes for gene delivery would be useful. The present study aimed to improve FasL gene therapy with a nonviral vector by taking advantage of the E3 and C1 domains of Del1 protein, which induces apoptosis and localizes to the extracellular matrix. METHODS: Mouse explanted tumors derived from a human oral squamous cell carcinoma cell line, SCCKN, were treated with plasmids encoding FasL (pFasL), E3C1 (pE3C1), and a fusion of FasL and E3C1 (pFasL-E3C1). The plasmids were injected locally every 7 days along with a transfection reagent, Jet-PEI (PolyPlus-transfection, San Marcos, CA, USA). RESULTS: All mice treated with a negative control plasmid or pFasL died within 49 days. By contrast, 83% of mice treated with pFasL-E3C1 survived longer than 49 days. Histochemical studies revealed that the fusion protein is localized to the stroma and induces apoptosis in stromal cells and adjacent parenchymal cells. CONCLUSIONS: The results obtained in the present study suggest that the protein deposition-based approach described, which makes use of the E3 and C1 domains of Del1, could comprise a novel method for cancer gene therapy with nonviral vectors.
BACKGROUND: The expression of FasL in cancer cells is currently being explored as a potential cancer therapy. Because high levels of FasL are necessary for effective treatment, current methods typically rely on the use of highly efficient viral vectors. However, because viral vector-based gene therapy is associated with certain risks, the development of effective nonviral routes for gene delivery would be useful. The present study aimed to improve FasL gene therapy with a nonviral vector by taking advantage of the E3 and C1 domains of Del1 protein, which induces apoptosis and localizes to the extracellular matrix. METHODS:Mouse explanted tumors derived from a humanoral squamous cell carcinoma cell line, SCCKN, were treated with plasmids encoding FasL (pFasL), E3C1 (pE3C1), and a fusion of FasL and E3C1 (pFasL-E3C1). The plasmids were injected locally every 7 days along with a transfection reagent, Jet-PEI (PolyPlus-transfection, San Marcos, CA, USA). RESULTS: All mice treated with a negative control plasmid or pFasL died within 49 days. By contrast, 83% of mice treated with pFasL-E3C1 survived longer than 49 days. Histochemical studies revealed that the fusion protein is localized to the stroma and induces apoptosis in stromal cells and adjacent parenchymal cells. CONCLUSIONS: The results obtained in the present study suggest that the protein deposition-based approach described, which makes use of the E3 and C1 domains of Del1, could comprise a novel method for cancer gene therapy with nonviral vectors.