纳米颗粒递送的自杀基因介导的结肠癌细胞在体外和体内的组织特异性细胞毒性
Tissue specific cytotoxicity of colon cancer cells mediated by nanoparticle-delivered suicide gene in vitro and in vivo.
作者信息
Zhang Guiying, Liu Ting, Chen Yong-Heng, Chen Yuxiang, Xu Meihua, Peng Jie, Yu Shuyi, Yuan Jianwei, Zhang Xiuwu
机构信息
Department of Gastroenterology, Xiangya Hospital, Central South University, Hunan Province, P.R. China.
出版信息
Clin Cancer Res. 2009 Jan 1;15(1):201-7. doi: 10.1158/1078-0432.CCR-08-1094.
PURPOSE
This study aimed to develop an efficient and safe strategy to introduce suicide genes into colon cancer cells.
EXPERIMENTAL DESIGN
In this study, we fused an enhanced carcinoembryonic antigen promoter (CEA) to a suicide gene, cytosine deaminase (CD). This construct was delivered into colon cancer cells using calcium phosphate nanoparticles (CPNP). The cells were then treated with the prodrug 5-FC. The therapeutic effect was evaluated in vitro and in vivo.
RESULTS
Our study showed that the CEA promoter-driven, CPNP-delivered suicide gene was only expressed in CEA-positive colon cancer cells, and resulted in significant cytotoxicity after administration of the prodrug 5-FC in vitro. Moreover, our in vivo study showed that CPNP-mediated CEA-CD delivery, together with 5-FC treatment, resulted in significant tumor growth delay in xenograft human colon carcinoma.
CONCLUSIONS
Our study indicates that the combination of CPNP and CEA-CD gene expression represents a novel approach for CEA-positive tumor gene therapy.
目的
本研究旨在开发一种高效且安全的策略，将自杀基因导入结肠癌细胞。
实验设计
在本研究中，我们将增强型癌胚抗原启动子（CEA）与自杀基因胞嘧啶脱氨酶（CD）融合。使用磷酸钙纳米颗粒（CPNP）将该构建体导入结肠癌细胞。然后用前药5-FC处理细胞。在体外和体内评估治疗效果。
结果
我们的研究表明，CEA启动子驱动、CPNP递送的自杀基因仅在CEA阳性结肠癌细胞中表达，并在体外给予前药5-FC后产生显著的细胞毒性。此外，我们的体内研究表明，CPNP介导的CEA-CD递送与5-FC治疗相结合，导致异种移植人结肠癌的肿瘤生长显著延迟。
结论
我们的研究表明，CPNP与CEA-CD基因表达的组合代表了一种针对CEA阳性肿瘤基因治疗的新方法。
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