Gene transduction for disseminated intraperitoneal tumor using cationic liposomes containing non-histone chromatin proteins: cationic liposomal gene therapy of carcinomatosa

Abstract

Cationic liposome-mediated gene therapy of cancer has been examined in a disseminated intraperitoneal tumor model. A combination of the strong CAG promoter–enhancer unit and high mobility group 1,2 (HMG-1,2) proteins has been used to improve transfection efficiency. The optimal deoxyribonucleic acid (DNA) and HMG-1,2 concentration ratio was determined in in vitro studies. Subsequently, we administered the liposome–DNA–HMG-1,2 complex intraperitoneally to tumor bearing nude mice and defined the most efficient concentration of liposomes. Using this approach, the median survival of tumor bearing nude mice was prolonged by the administration of a human tumor necrosis factor-α (TNF-α) gene inserted into a eukaryotic strong expression vector (pcagTNF-α) and exogenously added interferon-γ (INF-γ) (72 ± 3 days: mean ± s.e.). By contrast, survival was 36 ± 3, 39 ± 3 and 46 ± 4 days in groups receiving the TNF-α gene inserted in the reverse orientation (pcagTNF-αR) and normal saline (NS), pcagTNF-αR and INF-γ, and pcagTNF-α and NS, respectively. These results demonstrate an efficient approach for gene therapy of disseminated intraperitoneal cancer.