Soluble Flt-1 gene therapy for peritoneal metastases using HVJ-cationic liposomes

Many studies have reported a close association between VEGF and tumor angio genesis. The aim of the present study was to evaluate the effectiveness of gene therapy against cancer, including peritoneal metastasis, using a cDNA encoding a soluble type of Flt-1, one of the VEGF receptors. In a peritonea l metastasis model of MKN45 human gastric cancer cells, mice repetitively t reated with intraperitoneal injections of HVJ-Fex, a type of HVJ-cationic l iposome encapsulating a plasmid expressing soluble mFlt-1, exhibited smalle r disseminated foci with fewer microvessels, thus resulting in a significan tly longer survival period than the control mice. In another peritoneal met astasis model using HT1080S cells, a clone of HT1080 human fibrosarcoma cel ls stably transfected with hVEGF, treatments with HVJ-Fex also reduced the growth of disseminated foci without ascites formation. In conclusion, this study demonstrated that the peritoneal metastases of some cancers were larg ely dependent on VEGF, and that the repeated intraperitoneal transduction o f a soluble fit-1 gene using HVJ-cationic liposomes suppressed peritoneal m etastases, thereby contributing to a longer survival period.