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Antitum of Mechanism of Hybrid Liposomes and Clinical Application

杂化脂质体的抗癌作用机制及临床应用

基本信息

批准号：
12555232
负责人：
UEOKA Ryuichi
金额：
$ 6.4万
依托单位：
Sojo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

1. Antitumor Mechanism of Hybrid LiposomesWe examined mitochondrial pathway for apoptosis induced by hybrid liposomes. Mitochondrial membrane potential was decreased by adding hybrid liposomes, suggesting that hybrid liposomes should induce apoptosis through mitochondria. Release of cytochrome c and activation of caspase-9 were observed using western blotting analysis. Concentration dependence of caspase-9 inhibitor on the apoptotic DNA rates was also obtained. These results suggest that hybrid liposomes should induce apoptosis through mitochondria and activation of caspase-9.2. Inhibitory Effects of Three-Component Hybrid Liposomes Including Sugar SurfactantsWe successfully produced sugar-type micellar surfactants, lactonoalkylamide (LacCn), for the first time. Spherical vesicles, three-component hybrid liposomes, were obtained after sonication of mixture of L-α-dimyristoylphosphtidylcholine (DMPC), Tween 20 and LacCn (DMPC : Tween 20 : LacCn = 65 : 7 : 28). It is noteworthy that high … More inhibitory effects of the three-component hybrid liposomes composed of DMPC, Tween 20, and LacCn (DMPC : Tween 20 : LacCn = 65 : 7 : 28) on the growth ofglioma (U251) and lung adenocarcinoma (RERF-LC-OK) cells were attained in vitro without any drug, although no significant inhibitory effects of any individual component (DMPC, Tween 20, LacCn) or the two-component hybrid liposomes of DMPC and Tween 20 on the growth of tumor cells examined were obtained.3.Clinical Application of Hybrid LiposomesPatients with lymphoma were selected for the clinical application of hybrid liposomes composed of DMPC and C_<12>(EO)_<23> without any drug after passing the committee of bioethics. The hybrid liposomes were administered intravenously every day. There were not abnormal findings on routine blood test and hematochemistry. Prolonged survival was attained in patient with lymphoma after the intravenous injection of hybrid liposomes without any side effect and the remarkable reduction of neoplasm (solid tumor) was obtained after the local administration of hybrid liposomes. Such a successful clinical application of hybrid liposomes without drugs was for the first time in the world. Less

1.杂化脂质体的抗肿瘤机制我们研究了杂化脂质体诱导细胞凋亡的线粒体途径。加入杂化脂质体后，线粒体膜电位降低，提示杂化脂质体可能通过线粒体诱导细胞凋亡。用蛋白质印迹分析观察细胞色素c的释放和caspase-9的活化。caspase-9抑制剂对DNA凋亡率的浓度依赖性。这些结果表明，混合脂质体应通过线粒体和激活caspase-9.2诱导细胞凋亡。含糖表面活性剂的三组分杂化脂质体的抑制作用我们首次成功地合成了糖型胶束表面活性剂--内酯烷基酰胺（LacCn）。将L-α-二肉豆蔻酰磷脂酰胆碱（DMPC）、吐温20和LacCn（DMPC：吐温20：LacCn = 65：7：28）混合，超声处理后得到球形囊泡，即三组分混合脂质体。值得注意的是，高 ...更多信息 DMPC、Tween 20和LacCn组成的三组分混合脂质体的抑制作用（DMPC：吐温20：LacCn = 65：7：28）对胶质瘤（U251）和肺腺癌的生长抑制作用（RERF-LC-OK）细胞在没有任何药物的情况下在体外获得，尽管任何单个组分没有显著的抑制作用（DMPC，Tween 20，LacCn）或DMPC与Tween 20的双组分混合脂质体对肿瘤细胞生长的影响。3.混合脂质体的临床应用选择符合生物伦理学要求的淋巴瘤患者，在不加任何药物的情况下，应用DMPC与C_（EO）_组成的混合脂质体<12><23>。每天静脉内施用混合脂质体。血常规、血生化检查未见异常。淋巴瘤患者静脉注射复合脂质体后生存期延长，无任何副作用，局部注射复合脂质体后肿瘤（实体瘤）明显减少。这种无药物混合脂质体的成功临床应用在国际上尚属首次。少