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Inhibitory Effects of Hybrid Liposomes on the Growth of Tumor Cells along with Apoptosis Through the Activation of Caspases.

混合脂质体通过激活半胱天冬酶对肿瘤细胞生长和细胞凋亡的抑制作用。

基本信息

批准号：
17500323
负责人：
MATSUMOTO Yoko
金额：
$ 2.18万
依托单位：
Sojo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17500323/
关键词：
liposome apoptosis antitumor effect caspase chemotherapy breast tumor fluidity fusion

项目摘要

We have produced hybrid liposomes (HL) which can be prepared by sonication of vesicular and micellar molecules in a buffer solution. The physical properties of HL such as size, shape, membrane fluidity, and the temperature of phase separation can be controlled by changing the constituents and compositional ratio.We examined the effects of HL composed of dimyristoylphosphatidylcholine (DMPC) and 10mol% polyoxyethylenedodecyl ether (C_<12>(EO)_<23>) on the growth of human colon tumor cells (WiDr). It is worthy to note that a good correlation between the P values of 1,6-diphenyl-1,3,5-hecatriene incorporated into HL and fifty percent inhibitory concentration (IC_<50>) was obtained. This indicates that HL having larger fluidity could suppress greater the growth of tumor cells. HL distinguished between WiDr tumor cells and normal colon cells and then fused and accumulated into the membranes of WiDr cells leading to apoptosis. Activation of caspase-8,-9, and-3 was observed for WiDr cells after the treatment with HL, indicating that HL could apoptosis through the activation of caspase-8,-9, and-3. This study demonstrated that growth inhibition and apoptosis for tumor cells by HL provides the possibility of therapy from a viewpoint biophysical characteristics of tumor cell membrane.Highly inhibitory effects of HL on the growth of human breast tumor cells in vitro were obtained. Induction of apoptosis through the activation of caspases by HL was clearly obtained.HL induced apoptosis for human lymphoma cells in vitro. No toxicity was observed in the rats after intravenously injecting HL in vivo. We clearly demonstrated that a mouse model of lymphoma was established and prolonged survival was obtained in mice model of lymphoma after the treatment with HL without drugs in vivo.

我们已经产生了混合脂质体（HL），它可以通过在缓冲溶液中超声处理囊泡和胶束分子来制备。通过改变HL的组成和配比，可以控制HL的大小、形状、膜流动性和相分离温度等物理性质，本文研究了由二肉豆蔻酰磷脂酰胆碱（DMPC）和10mol%聚氧乙烯十二烷基醚（C_<12>（EO）_<23>）组成的HL对人结肠癌细胞（WiDr）生长的影响。值得注意的是，1，6-二苯基-1，3，5-hecatriene掺入HL的P值与50%抑制浓度（IC）之间具有良好的相关性<50>。这表明具有较大流动性的HL可以更好地抑制肿瘤细胞的生长。HL区分WiDr肿瘤细胞和正常结肠细胞，然后融合并积聚到WiDr细胞的膜中，导致凋亡。HL处理后，观察到WiDr细胞的caspase-8、-9和-3活化，表明HL可以通过caspase-8、-9和-3的活化而凋亡。本研究从肿瘤细胞膜生物物理特性的角度证明HL对肿瘤细胞的生长抑制和凋亡为治疗肿瘤提供了可能，并在体外实验中获得了HL对人乳腺癌细胞生长的高度抑制作用。HL可通过激活caspase而诱导细胞凋亡。HL在体外可诱导人淋巴瘤细胞凋亡。HL在大鼠体内静脉注射未见毒性反应。我们清楚地表明，建立了小鼠淋巴瘤模型，并在体内用HL无药物治疗后，在小鼠淋巴瘤模型中获得了延长的生存期。