The use of folate-PEG-grafted-hybranched-PEI nonviral vector for the inhibition of glioma growth in the rat
The use of folate-PEG-grafted-hybranched-PEI nonviral vector for the inhibition of glioma growth in the rat
复制标题
叶酸-PEG-接枝-杂交-PEI非病毒载体用于抑制大鼠神经胶质瘤生长的用途
DOI：
10.1016/j.biomaterials.2009.04.011
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发表时间：
2009-08-01
期刊：
影响因子：
14
通讯作者：
Peng, Ying
中科院分区：
文献类型：
--
作者：
Liang, Bing;He, Ming-Liang;Peng, Ying
已提出使用非病毒剂介导的酶/前药疗法和免疫疗法的联合治疗作为癌症治疗的强大替代方法。本研究旨在评估胞嘧啶脱氨酶/5-氟胞嘧啶（CD/5-FC）和TNF相关凋亡诱导配体（TRAIL）基因联合用于对抗大鼠C6胶质瘤细胞的体外细胞毒性和体内治疗效果。在 FR 表达的 C6 神经胶质瘤细胞和 Wistar 大鼠中测试了用作非病毒载体的 FA-PEG-PEI 的效力。采用FA-PEG-PEI/pCD/5-FC和FA-PEG-PEI/pTRAIL联合应用治疗C6胶质瘤细胞和动物模型。通过存活测定和肿瘤体积评估抗肿瘤效果。这项研究表明，在 C6 胶质瘤细胞中联合应用 FA-PEG-PEI/pCD/5-FC 和 FA-PEG-PEI/pTRAIL 治疗后，体外细胞毒性显着增加。动物研究表明，联合治疗可显着抑制 C6 神经胶质瘤异种移植物的生长。这些结果表明，联合治疗在体外和体内条件下对 C6 神经胶质瘤细胞产生附加的细胞毒性作用，并表明这种使用酶/前药疗法和 TRAIL 免疫疗法的治疗方法可能是治疗神经胶质瘤的一种有前途的治疗策略。 (C) 2009 Elsevier Ltd. 保留所有权利。
Combined treatment using nonviral agent-mediated enzyme/prodrug therapy and immunotherapy had been proposed as a powerful alternative method of cancer therapy. The present study was aimed to evaluate the cytotoxicity in vitro and the therapeutic efficacy in vivo when the cytosine deaminase/5-fluorocytosine (CD/5-FC) and TNF-related apoptosis-inducing ligand (TRAIL) genes were jointly used against rat C6 glioma cells. The potency of the FA-PEG-PEI used as a nonviral vector was tested in the FR-expressed C6 glioma cells and Wistar rats. The C6 glioma cells and animal model were treated by the combined application of FA-PEG-PEI/pCD/5-FC and FA-PEG-PEI/pTRAIL. The antitumor effect was evaluated by survival assays and tumor volume. This study revealed a significant increase of cytotoxicity in vitro following the combined application of FA-PEG-PEI/pCD/5-FC and FA-PEG-PEI/pTRAIL treatments in C6 glioma cells. Animal studies showed a significant growth inhibition of the C6 glioma xenografts using the combined treatment. These results demonstrated that the combined treatment generated additive cytotoxic effect in C6 glioma cells in both in vitro and in vivo conditions, and indicated that such treatment method using both enzyme/prodrug therapy and TRAIL immunotherapy might be a promising therapeutic strategy in treating glioma. (C) 2009 Elsevier Ltd. All rights reserved.