Specific Inhibitory Effects of Hybrid Liposomes on the Growth of Various Tumor Cells

杂化脂质体对多种肿瘤细胞生长的特异性抑制作用

基本信息

批准号：
10680811
负责人：
MATSUMOTO Yoko
金额：
$ 1.79万
依托单位：
Kumamoto Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10680811/
关键词：
lipsome chemotherapy fusion apoptosis

项目摘要

1. Inhibitory Effects of Hybrid Liposomes on the Growth of tumor Cells in vitroThe 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 LiposomesWe 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 MelanomatosisA 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.

1. Inhibitory Effects of Hybrid Liposomes on the Growth of Tumor Cells in vitroThe 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, 2-二羟基酯-3-三甲基丙烷（DMTAP））和多氧乙烯（10）十二烷基醚（CII D212E D2（EO）II D210E D2）对肿瘤细胞的生长（人类肺癌（RERF-LC-OK），人类Hepatoma（Human Hepattom）（Human HepaT）（Human Hepcan）（Hep Chn），Hep-gn3检查了体外。具有DMPG/10MOL％（CII D212E D2（EO）II D210E D2）组成的杂化脂质体的高度特异性抑制作用对RERF-LC-OK和GT3TKB生长的高度特异性抑制作用，这一点吸引人。诱导凋亡杂交脂质体We研究了由二吡莫氏二磷脂酰胆碱和多氧乙基乙醚组成的杂化脂质体的抗肿瘤机制，其抑制性作用抑制与肿瘤细胞相关的生长。杂交脂质体在HL-60细胞中诱导凋亡的凋亡是根据DNA的琼脂糖凝胶电泳和流式细胞仪分析的，并使用碘化丙旋纤维细胞仪进行了验证。使用异硫氰酸荧光素作为荧光探针拍摄的荧光显微照片，表明杂交脂质体应与肿瘤细胞膜融合。融合后，根据DNA分析揭示了杂交脂质体向肿瘤细胞膜的积累。3。通过腹膜内接种刘易斯肺癌细胞的接种，用杂种脂质体的化学疗法用于黑色素瘤小鼠的肺癌模型。通过将杂化脂质体给小鼠施用，可延长生存期（480％）。该结果表明，杂化脂质体应有效地治疗癌症。此外，在体内的正常大鼠中，未获得杂化脂质体的毒性，没有副作用。