Effect of transfection of tumor necrosis factor α gene and its mutants on tumorigenicity of H22 tumor cells in vivo

AIM: To compare the tumorigenecity of H22 cells transfected with TNF-α gene and its mutants (secreted TNF-α mutant, S-TNFm, transmembrane TNF-α mutant, TM-TNFm and wild type of TNF-α, Wt-TNF) in vivo . METHODS: Three kinds of mouse liver cancer cell line H22 expressing TNF-α and its two mutants were mixed with untransfected H22 at different effector/target ratio separately. The growth of tumor was examined after injection of 2.5×10 5 (100 μL) mixed H22 tumor cells into mice. The lymphocyte infiltration in the site of tumor and the expression of Fas on tumor cells were detected by immunohistochemistry. RESULTS: The tumorigenecity of H22 cells transfected with TNF-α gene and its mutants was significantly weakened ( P 0.01). Besides the cytotoxicity of the both forms of TNF, TM-TNF was found to induce the expression of death receptor Fas by tumor cells and S-TNF was shown to promote frank lymphocyte infiltration in the site of tumor. Furthermore, a transient decrease in body weight was found in mice inoculated with H22/S-TNFm. CONCLUSION: The tumorigenecity of tumor cells was reduced by transfection with TM-TNF or S-TNF gene. It results from the cytotoxicity of TNF and their activation of tumorcidal mechanisms in vivo . TM-TNF may induce tumor cell apoptosis via the Fas pathway while S-TNF may exert its antitumor effect by recruiting and activating lymphocytes in the site of tumor.