1999 Fiscal Year Final Research Report Summary
Specific Inhibitory Effects of Hybrid Liposomes on the Growth of Various Tumor Cells
| Project/Area Number |
10680811
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | Kumamoto Institute of Technology |
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Principal Investigator |
MATSUMOTO Yoko Kumamoto Institute of Technology, Associate Professor, 工学部, 助教授 (00133562)
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| Co-Investigator(Kenkyū-buntansha) |
KANNO Akihiro Panapharm Laboratories, Researcher, 研究員
UEOKA Ryuichi Kumamoto Institute of Technology, Professor, 工学部, 教授 (70099076)
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| Project Period (FY) |
1998 – 1999
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| Keywords | lipsome / chemotherapy / fusion / apoptosis |
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| Research Abstract |
1. Inhibitory Effects of Hybrid Liposomes on the Growth of tumor Cells in vitro
The inhibitory effects of hybrid liposomes composed of lipids having a variety of head groups (zwitterionic L-α-dimyristoylphosphatidylcholine (DMPC), anionic L α-dimyristoylphosphatidyl glycerol (DMPG) and cationic 1, 2-dimyristoyl-3-trimethylammonium propane (DMTAP)) and polyoxyethylene (10) dodecyl ether (CィイD212ィエD2(EO)ィイD210ィエD2) on the growth of tumor cells (human lung carcinoma (RERF-LC-OK), human hepatoma (Hep-G2), human stomach tumor (GT3TKB)) in vitro were examined. It is attractive that the highly specific inhibitory effect of the hybrid liposomes composed of DMPG/10mol% (CィイD212ィエD2(EO)ィイD210ィエD2) On the growth of RERF-LC-OK and GT3TKB was obtained without any antitumor drugs.
2. Induction of Apoptosis Hybrid Liposomes
We examined antitumor mechanism of the hybrid liposomes composed of dimyristoylphosphatidylcholine and polyoxyethylenealkyl ether having inhibitory action toward the growth of tumor cells related to apoptosis. The induction of apoptosis by the hybrid liposomes in HL-60 cells was verified on the basis of agarose gel electrophoresis of DNA and flow cytometry analysis with the propidium iodide staining method. A fluorescence micrograph taken using fluorescein isothiocyanate as a fluorescence probe showed that the hybrid liposomes should fuse with the tumor cell membrane. After fusion, accumulation of the hybrid liposomes to tumor cell membrane was revealed on the basis of DNA analysis.
3. Chemotherapy with Hybrid Liposomes for Melanomatosis
A mouse model of lung carcinoma was established by intraperitoneal inoculate of Lewis lung carcinoma cells. The remarkably prolonged survival (480%) was attained by administering the hybrid liposomes to mice. This result suggests that the hybrid liposomes should be effective for the treatment of cancers. Furthermore, no toxicity of the hybrid liposomes was obtained in normal rats in vivo with no side effects.
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