Local delivery system of cytotoxic agents to tumors by focused sonoporation.
Cancer Gene Ther
; 14(4): 354-63, 2007 Apr.
Article
em En
| MEDLINE
| ID: mdl-17273182
ABSTRACT
Recently, ultrasound-targeting microbubble destruction has been employed in molecular gene therapy, and a new potent nonviral gene transfer method known as 'sonoporation' has been developed. We investigated the efficiency of sonoporation toward growth inhibition of human gingival squamous carcinoma cell line, Ca9-22, in vitro and in vivo. The cytotoxicity of bleomycin (BLM) was investigated using flow-cytometric analysis and Hoechst's staining in vitro assay systems. We found that the delivery of BLM by sonoporation induced cytotoxic effect toward Ca9-22 cells in vitro. Our in vivo results showed that tumors nearly disappeared in Ca9-22 cell-implanted nude KSN/slc mice treated with a low dose of BLM followed by sonoporation during the 4-week experimental period. Histological analysis revealed that the cytotoxic effect was mainly apoptosis. We previously reported that the cytolethal distending toxin B (cdtB) from Actinobacillus actinomycetemcomitans, a periodontopathic bacterium, is responsible for cell cycle arrest and apoptosis in vitro. Thus, we used sonoporation to transfect a cdtB-expressing plasmid into Ca9-22 cells and examined cell viability in vitro and in vivo. We found that an administration of cdtB-expressing plasmid followed by sonoporation-induced marked growth inhibition of Ca9-22 cells and apoptotic cells were also observed in vitro and in vivo. These findings suggest that local administration of cytotoxic agents with sonoporation is a useful method for molecular cancer therapy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxinas Bacterianas
/
Ultrassom
/
Bleomicina
/
Neoplasias Gengivais
/
Carcinoma de Células Escamosas
/
Terapia Genética
/
Sistemas de Liberação de Medicamentos
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Gene Ther
Assunto da revista:
GENETICA MEDICA
/
NEOPLASIAS
/
TERAPEUTICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Japão