Tissue specific cytotoxicity of colon cancer cells mediated by nanoparticle-delivered suicide gene in vitro and in vivo.
OBJECTIVE
This study aimed to develop an efficient and safe strategy to introduce suicide genes into colon cancer cells.


METHODS
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.
Zhang
Guiying
G
Department of Gastroenterology, Xiangya Hospital, Central South University, Hunan Province, P.R. China. zhangguiying2007@gmail.com
Liu
Ting
T
Chen
Yong-Heng
YH
Chen
Yuxiang
Y
Xu
Meihua
M
Peng
Jie
J
Yu
Shuyi
S
Yuan
Jianwei
J
Zhang
Xiuwu
X
D000818:Animals; D017209:Apoptosis; D002130:Calcium Phosphates; D002272:Carcinoembryonic Antigen / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D043525:Cytosine Deaminase / Q000235:genetics*; D005472:Fluorouracil / Q000627:therapeutic use; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D011401:Promoter Regions, Genetic; D023041:Xenograft Model Antitumor Assays
D002130:Calcium Phosphates; D002272:Carcinoembryonic Antigen; C020243:calcium phosphate; D043525:Cytosine Deaminase; D005472:Fluorouracil