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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.杂合脂质体对肿瘤细胞体外生长的抑制作用--由多种头基脂质组成的杂合脂质体的抑制作用（两性离子L-α-二肉豆蔻酰磷脂酰胆碱（DMPC）、阴离子L α-二肉豆蔻酰磷脂酰甘油（DMPG）和阳离子1，2-二肉豆蔻酰基-3-三甲基铵丙烷（DMTAP））和聚氧乙烯（10）十二烷基醚检测了（CイD212 D2（EO）イD210 D2）对体外肿瘤细胞（人肺癌（RERF-LC-OK）、人肝癌（Hep-G2）、人胃肿瘤（GT 3 TKB））生长的影响。DMPG/10mol%（C/D 212/D 2（EO）/D 210/D 2）复合脂质体对RERF-LC-OK和GT3 TKB的生长具有高度特异性的抑制作用，且不含任何抗肿瘤药物.诱导细胞凋亡的杂化脂质体我们研究了由二肉豆蔻酰磷脂酰胆碱和聚氧乙烯烷基醚组成的杂化脂质体的抗肿瘤机制，该杂化脂质体对与细胞凋亡相关的肿瘤细胞的生长具有抑制作用。DNA琼脂糖凝胶电泳和碘化丙啶染色流式细胞仪分析证实了杂交脂质体诱导HL-60细胞凋亡的作用。用异硫氰酸荧光素作为荧光探针拍摄的荧光显微照片显示，杂交脂质体应与肿瘤细胞膜融合。融合后，DNA分析显示杂交脂质体在肿瘤细胞膜上的聚集.杂交脂质体治疗黑色素瘤的研究通过腹腔接种刘易斯肺癌细胞建立小鼠肺癌模型。小鼠的存活率显著延长（480%）。这一结果表明，杂交脂质体应该是有效的治疗癌症。此外，在正常大鼠体内没有获得杂化脂质体的毒性，没有副作用。