Development of the next-generation therapy for cancer using sonoporation, and clinical application
| Project/Area Number |
17390542
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Kyushu Dental College |
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Principal Investigator |
FUKUDA Jinichi Kyushu Dental College, Dentistry, Professor, 歯学部, 教授 (00106270)
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| Co-Investigator(Kenkyū-buntansha) |
TOMINAGA Kazuhiro Kyushu Dental College, Dentistry, Assistant Professor, 歯学部, 助教授 (40188793)
NISHIHARA Tatsuji Kyushu Dental College, Dentistry, Professor, 歯学部, 教授 (80192251)
TSUJISAWA Toshiyuki Kyushu Dental College, Dentistry, Assistant, 歯学部, 助手 (60265006)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2006: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2005: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | sonoporation / squamous cell carcinoma / apoptosis / in vivo transfection / microbubble / 口腔扁平上皮癌 |
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| Research 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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Report
(3 results)
Research Products
(17 results)
