1. ¹Department of Surgery II, Nagoya University School of Medicine, Nagoya 466-8550, Japan
2. ²Department of Surgery, National East Nagoya Hospital, Nagoya 465-8620, Japan
3. ³Department of Surgery, National Toyohashi Hospital, Toyohashi 441-8585, Japan
4. ⁴Department of Equipment Center for Research and Education, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
5. ⁵Department of Anatomy, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan

Correspondence: Dr Yoshikazu Sakakima, Department of Surgery II, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: sakakima@med.nagoya-u.ac.jp

Received 6 October 2004; Published online 13 May 2005.

Abstract

We examined whether sonoporation enhanced by a contrast agent (BR14) was effective in gene therapy for hepatocelluar carcinoma (HCC). Human hepatic cancer cells (SK-Hep1) and plasmid cDNAs expressing green fluorescent protein (GFP), interferon (IFN), and LacZ were used. In vitro, SK-Hep1 cell suspensions with DNA and BR14 were sonoporated. Expressions of every plasmid cDNA and the antitumor effect of IFN were analyzed. In vivo, GFP and IFN genes with BR14 were directly injected into subcutaneous tumors using SK-Hep1 in nude mice, and transcutaneous sonoporation of the tumors was performed. GFP gene transfections and tumor diameters after IFN gene transfection were examined. In vitro, no SK-Hep1 cells were transfected without sonication, whereas transfections were successful after sonication with BR14. Antitumor effect of IFN gene transfection by ultrasound (US) and with BR14 was revealed. In vivo, the SK-Hep1 cells expressed GFP, and the IFN gene transfection by US with BR14 reduced tumor size significantly. In conclusion, gene therapy with sonoporation enhanced by a contrast agent may become a new treatment option for HCC.