Effect of sonoporation on cationic liposome-mediated IFNbeta 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 (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.
Hayashi
S
S
Department of Neurosurgery, Nagoya University, Graduate School of Medicine, 65 Tsurumai, [corrected] Showa-ku, Nagoya, Japan. shuji1@mba.ocn.ne.jp
Mizuno
M
M
Yoshida
J
J
Nakao
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D015316:Genetic Therapy / Q000379:methods*; D016899:Interferon-beta / Q000008:administration & dosage*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000556:secondary / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D019076:Transgenes; D014463:Ultrasonography
D000970:Antineoplastic Agents; D008081:Liposomes; D016899:Interferon-beta; D002945:Cisplatin