Effect of sonoporation on cationic liposome-mediated IFNβ gene therapy for metastatic hepatic tumors of murine colon cancer

To examine the efficacy of ultrasound-mediated gene therapy in the treatment of hepatic cancer, we performed cationic liposome-mediated interferon-beta (IFN beta) gene therapy combined with sonoporation, using metastatic hepatic tumors of murine colon cancer. The combination of liposome/DNA treatment and ultrasound gave higher transgene IFN beta expression in Colon26 colon adenocarcinoma cells than that with microbubble/DNA in combination with ultrasound and that with liposome/DNA alone. Cationic liposome-mediated IFN beta gene therapy combined with ultrasound showed an antitumor effect in vitro and combination use of the anticancer drug cis-diamminedichloroplatinum (CDDP) showed a synergistic effect with the IFN beta gene therapy. The survival of mice with metastatic hepatic tumor of Colon26 cells was significantly prolonged by cationic liposome-mediated IFN beta gene therapy alone, and sonoporation had a synergistic effect on prolongation of survival and inhibition of tumor growth rate in these mice. Combination use of CDDP with IFN beta gene therapy also showed a synergistic effect on prolongation of survival and inhibition of tumor growth rate. In conclusion, ultrasound-mediated gene therapy for the treatment of hepatic cancers may be effective in a clinical setting. Cancer Gene Therapy (2009) 16, 638-643; doi:10.1038/cgt.2008.1; published online 5 June 2009