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

我们制备了一种杂化脂质体（HL），它可以通过在缓冲溶液中对囊泡和胶束分子进行超声处理来制备。通过改变HL的组分和组成比，可以控制HL的尺寸、形状、膜流动性和相分离温度等物理性质。研究了二肉豆醇酰基磷脂酰胆碱（DMPC）和10mol%聚氧乙烯十二烷基醚（C_<12>(EO)_<23>）组成的HL对人结肠癌肿瘤细胞（WiDr）生长的影响。值得注意的是，掺入HL的1,6-二苯基-1,3,5-己三烯的P值与50%的抑制浓度（IC_<50>）之间具有良好的相关性。说明流动性越大的HL对肿瘤细胞的抑制作用越大。HL区分了WiDr肿瘤细胞和正常结肠细胞，融合并积聚在WiDr细胞的细胞膜上导致细胞凋亡。HL处理后，WiDr细胞中caspase-8、-9和3活化，说明HL可通过caspase-8、-9和3活化而凋亡。本研究表明，从肿瘤细胞膜的生物物理特性来看，HL对肿瘤细胞的生长抑制和凋亡提供了治疗的可能性。在体外实验中，HL对人乳腺肿瘤细胞的生长有高度的抑制作用。HL通过激活半胱天冬酶诱导细胞凋亡。HL诱导人淋巴瘤细胞体外凋亡。大鼠体内静脉注射HL后未见毒性反应。我们清楚地证明了建立了小鼠淋巴瘤模型，并且在体内不使用药物的情况下，HL治疗后的小鼠淋巴瘤模型存活时间延长。

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.