The antitumour activities induced by pegylated liposomal cytochalasin D in murine models
The antitumour activities induced by pegylated liposomal cytochalasin D in murine models
复制标题
聚乙二醇化脂质体细胞松弛素 D 在小鼠模型中诱导的抗肿瘤活性
DOI：
10.1016/j.ejca.2011.12.018
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发表时间：
2012-09-01
影响因子：
8.4
通讯作者：
Lin, Ying-ying
中科院分区：
文献类型：
--
作者：
Huang, Feng-ying;Mei, Wen-li;Lin, Ying-ying
细胞松弛素D作用于肌动蛋白，在真核细胞中普遍存在。当细胞松弛素D作为细胞毒性剂用于癌症治疗时，会引发显著的副作用。为避免这一情况，可将细胞松弛素D包裹在聚乙二醇脂质体中。在本研究中，通过高效液相色谱法对聚乙二醇化脂质体细胞松弛素D在荷瘤小鼠体内的生物分布进行观察，结果显示脂质体细胞松弛素D可方便地溶解于水中用于静脉注射，且相较于天然细胞松弛素D，它能特异性地在肿瘤组织中积聚。脂质体细胞松弛素D在血浆中的半衰期也显著长于天然细胞松弛素D（4小时对比10分钟）。MTT（3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴化物）检测表明，脂质体细胞松弛素D在体外对细胞增殖的抑制作用与天然细胞松弛素D相似，效果显著。在B16黑色素瘤、CT26结直肠癌和H22肝癌模型中对脂质体细胞松弛素D的抗肿瘤活性进行了研究，结果表明脂质体细胞松弛素D能以与顺铂相似的方式显著抑制肿瘤生长并延长生存期。基于TUNEL的细胞凋亡检测显示，脂质体细胞松弛素D可诱导显著的肿瘤细胞凋亡。观察发现，接受脂质体细胞松弛素D治疗的小鼠肿瘤血管生成受到显著抑制。此外，接受脂质体细胞松弛素D治疗的小鼠未出现明显副作用。我们的研究结果表明，脂质体细胞松弛素D提高了溶解度和生物利用度，降低了副作用发生率，并增强了抗肿瘤效果，这表明其具有作为癌症治疗化学药物的潜力。（C）2011爱思唯尔有限公司版权所有。
Cytochalasin D targets actin and is ubiquitous in eukaryotic cells. When cytochalasin D is used as a cytotoxic agent in cancer therapy, it causes significant side effects. To prevent this, cytochalasin D can be encapsulated in polyethylene liposomes. In this study, high-performance liquid chromatography observation of the biodistribution of pegylated liposomal cytochalasin D in tumour-bearing mice showed that liposomal cytochalasin D could be conveniently dissolved in water for i.v. injection and that it specifically accumulated in tumour tissues, more than natural cytochalasin D did. The half-time of liposomal cytochalasin D in the plasma was also significantly longer than that of natural cytochalasin D (4 h versus 10 min). MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that liposomal cytochalasin D treatment could cause significant inhibition of cell proliferation in vitro in a manner similar to that of natural cytochalasin D. The antitumour activities of liposomal cytochalasin D were investigated in B16 melanoma, CT26 colorectal carcinoma and H22 hepatoma models, and the results indicated that liposomal cytochalasin D could significantly inhibit tumour growth and prolong survival in a manner similar to that of cisplatin. TUNEL-based apoptosis assays showed that liposomal cytochalasin D induced significant tumour cell apoptosis. Significant inhibition of tumour angiogenesis was observed in mice treated with liposomal cytochalasin D. In addition, no significant side effects were observed in mice treated with liposomal cytochalasin D. Our results show that liposomal cytochalasin D increases solubility and bioavailability, a lower incidence of side effects and improves antitumour effects, indicating its potential as a chemical agent for cancer therapy. (C) 2011 Elsevier Ltd. All rights reserved.