Original Article

Cancer Gene Therapy (2009) 16, 638–643; doi:10.1038/cgt.2008.1; published online 5 June 2009

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

S Hayashi1, M Mizuno2, J Yoshida2 and A Nakao3

  1. 1Department of Advanced Medicine in Biotechnology and Robotics, Nagoya University, School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Japan
  2. 2Department of Neurosurgery, Nagoya University, School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Japan
  3. 3Department of Surgery, Nagoya University, School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Japan

Correspondence: Dr S Hayashi, Department of Advanced Medicine in Biotechnology and Robotics, Nagoya University, School of Medicine, 13-8 Takamine-cho, Showa-ku, Nagoya 466-0811, Japan. E-mail: shuji1@mba.ocn.ne.jp

Received 31 October 2006; Revised 8 June 2007; Accepted 29 July 2007; Published online 5 June 2009.

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Abstract

To examine the efficacy of ultrasound-mediated gene therapy in the treatment of hepatic cancer, we performed cationic liposome-mediated interferon-beta (IFNbeta) gene therapy combined with sonoporation, using metastatic hepatic tumors of murine colon cancer. The combination of liposome/DNA treatment and ultrasound gave higher transgene IFNbeta expression in Colon26 colon adenocarcinoma cells than that with microbubble/DNA in combination with ultrasound and that with liposome/DNA alone. Cationic liposome-mediated IFNbeta 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 IFNbeta gene therapy. The survival of mice with metastatic hepatic tumor of Colon26 cells was significantly prolonged by cationic liposome-mediated IFNbeta 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 IFNbeta 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.

Keywords:

sonoporation, ultrasound, liposome, IFNbeta, hepatic metastases

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