In vitro and in vivo double-enhanced suicide gene therapy mediated by generation 5 polyamidoamine dendrimers for PC-3 cell line

World Journal of Surgical Oncology

Research

Ranlu Liu¹  Yong Xu¹  Yue Chen¹  Zhihong Zhang¹  Kuo Yang¹  Gang Wang²  Weiming Zhao³  Deling Kong⁴ 

[1] Department of Urology, Second Hospital of TianJin Medical University, TianJin Institute of Urology, Tianjin, China;Department of Urology, Second Hospital of TianJin Medical University, TianJin Institute of Urology, Tianjin, China;Department of Urology, HeBei General Hospital, Shijiazhuang, HeBei province, China;Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China;The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, China;

关键词: Prostate Cancer;    Gemcitabine;    Bystander Effect;    Suicide Gene;    Herpes Simplex Virus Thymidine Kinase;   

DOI  :  10.1186/1477-7819-10-3

 received in 2011-10-08, accepted in 2012-01-08,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundOne of the most frequently used and efficient suicide gene therapies for prostate cancer is HSV-TK/GCV system, but its application has been limited due to lack of favorable gene vector and the reduction of "bystander effect". We investigated the effect of a novel combination of HSV-TK/GCV fused with Cx43 and gemcitabine using non-viral vector generation 5 polyamidoamine dendrimers (G5-PAMAM-D) on PC-3 cells.MethodsRT-PCR and Western blot were used to detect TK and Cx43 expression. Cell viability and proliferation were measured by using MTT assay. Cell apoptosis was detected with double-staining of Annexin V-FITC and propidium iodide (PI) by flow cytometry. Nude mice models were established to evaluate the therapeutic effect in vivo.ResultsG5-PAMAM-D efficiently delivered recombinant plasmids into PC-3 cells and HSV-TK and Cx43 could be expressed successfully. With gemcitabine, G5-PAMAM-D mediated HSV-TK and Cx43 expression effectively inhibited prostate cancer PC-3 cell proliferation, leading to more cellular apoptosis and inhibiting PC-3 tumor growth in nude mice models.ConclusionsThis study illustrates that this new suicide gene system mediated by G5-PAMAM-D is effective in decreasing PC-3 cell proliferation and inducing cell apoptosis, and inhibiting tumor growth in vivo. In a word, our study could provide a potential approach for gene therapy of prostate cancer.

【 授权许可】

Unknown   
© Chen et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.