Sakakima Yoshikazu, Hayashi Shuji, Yagi Yoshikazu, Hayakawa Akemi, Tachibana Katsuro, Nakao Akimasa
Department of Surgery II, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
Cancer Gene Ther. 2005 Nov;12(11):884-9. doi: 10.1038/sj.cgt.7700850.
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), interferonbeta (IFNbeta), 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 IFNbeta were analyzed. In vivo, GFP and IFNbeta 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 IFNbeta 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 IFNbeta gene transfection by ultrasound (US) and with BR14 was revealed. In vivo, the SK-Hep1 cells expressed GFP, and the IFNbeta 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.
我们研究了由造影剂（BR14）增强的声孔效应在肝细胞癌（HCC）基因治疗中是否有效。使用了人肝癌细胞（SK-Hep1）以及表达绿色荧光蛋白（GFP）、干扰素β（IFNβ）和LacZ的质粒cDNA。在体外，对含有DNA和BR14的SK-Hep1细胞悬液进行声孔效应处理。分析了每种质粒cDNA的表达以及IFNβ的抗肿瘤作用。在体内，将携带BR14的GFP和IFNβ基因直接注射到裸鼠皮下的SK-Hep1肿瘤中，并对肿瘤进行经皮声孔效应处理。检测了GFP基因转染情况以及IFNβ基因转染后的肿瘤直径。在体外，未超声处理时没有SK-Hep1细胞被转染，而用BR14进行超声处理后转染成功。揭示了超声（US）联合BR14进行IFNβ基因转染的抗肿瘤作用。在体内，SK-Hep1细胞表达了GFP，超声联合BR14进行IFNβ基因转染显著减小了肿瘤大小。总之，由造影剂增强声孔效应的基因治疗可能成为HCC的一种新的治疗选择。
