Hayashi S, Mizuno M, Yoshida J, Nakao A
Department of Neurosurgery, Nagoya University, Graduate School of Medicine, 65 Tsurumai, [corrected] Showa-ku, Nagoya, Japan.
Cancer Gene Ther. 2009 Aug;16(8):638-43. doi: 10.1038/cgt.2008.1. Epub 2009 Jun 5.
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.
为了研究超声介导的基因治疗在肝癌治疗中的疗效，我们使用小鼠结肠癌转移性肝肿瘤，进行了阳离子脂质体介导的β-干扰素（IFNβ）基因治疗并联合声穿孔。脂质体/DNA处理与超声联合使用时，在Colon26结肠腺癌细胞中产生的转基因IFNβ表达高于微泡/DNA与超声联合使用以及单独使用脂质体/DNA时。阳离子脂质体介导的IFNβ基因治疗联合超声在体外显示出抗肿瘤作用，抗癌药物顺二氯二氨铂（CDDP）与IFNβ基因治疗联合使用显示出协同作用。单独使用阳离子脂质体介导的IFNβ基因治疗可显著延长携带Colon26细胞转移性肝肿瘤小鼠的生存期，声穿孔对延长这些小鼠的生存期和抑制肿瘤生长速度具有协同作用。CDDP与IFNβ基因治疗联合使用在延长生存期和抑制肿瘤生长速度方面也显示出协同作用。总之，超声介导的基因治疗在临床环境中治疗肝癌可能是有效的。
