Adenovirus-mediated delivery of interferon-γ gene inhibits the growth of nasopharyngeal carcinoma

Journal of Translational Medicine

Research

Liang Kang¹  Huan-xin Lin²  Jiang-xue Wu²  Lan-cai Zhu²  Ling Zhou²  Ying-hui Zhu²  Hong-yu Han²  Ran-yi Liu²  Hong-li Li³  Peng Zhao⁴  Wenlin Huang⁵ 

[1] Department of Colorectal Surgery, the Sixth Affliated Hospital, Sun Yat-sen University, 510655, Guangzhou, China;State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dong-feng Road East, 510060, Guangzhou, China;State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dong-feng Road East, 510060, Guangzhou, China;Department of Gastrointestinal Oncology, Tianjin Medical University Cancer Institute and Hospital, 300060, Tianjin, China;State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dong-feng Road East, 510060, Guangzhou, China;Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, Hangzhou, China;State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dong-feng Road East, 510060, Guangzhou, China;Institute of Microbiology, Chinese Academy of Science, 100101, Beijing, China;Guangdong Provincial Key Laboratory of Tumor-targeted Drug, Guangzhou Doublle Bioproducts Co., Ltd., 510663, Guangzhou, China;

关键词: Gene therapy;    Interferon-γ;    Nasopharyngeal carcinoma;    Adenoviral vector;   

DOI  :  10.1186/1479-5876-10-256

 received in 2012-10-25, accepted in 2012-12-17,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundInterferon-γ (IFN-γ) is regarded as a potent antitumor agent, but its clinical application is limited by its short half-life and significant side effects. In this paper, we tried to develop IFN-γ gene therapy by a replication defective adenovirus encoding the human IFN-γ (Ad-IFNγ), and evaluate the antitumoral effects of Ad-IFNγ on nasopharyngeal carcinoma (NPC) cell lines in vitro and in xenografts model.MethodsThe mRNA levels of human IFN-γ in Ad-IFNγ-infected NPC cells were detected by reverse transcription-polymerase chain reaction (RT-PCR), and IFN-γ protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in the culture supernatants of NPC cells and tumor tissues and bloods of nude mice treated with Ad-IFNγ. The effects of Ad-IFNγ on NPC cell proliferation was determined using MTT assay, cell cycle distribution was determined by flow cytometry analysis for DNA content, and cells apoptosis were analyzed by Annexin V-FITC/7-AAD binding assay and hoechst 33342/PI double staining. The anti-tumor effects and toxicity of Ad-IFNγ were evaluated in BALB/c nude mice carrying NPC xenografts.ResultsThe results demonstrated that Ad-IFNγ efficiently expressed human IFN-γ protein in NPC cell lines in vitro and in vivo. Ad-IFNγ infection resulted in antiproliferative effects on NPC cells by inducing G1 phase arrest and cell apoptosis. Intratumoral administration of Ad-IFNγ significantly inhibited the growth of CNE-2 and C666-1 cell xenografts in nude mice, while no significant toxicity was observed.ConclusionsThese findings indicate IFN-γ gene therapy mediated by replication defective adenoviral vector is likely a promising approach in the treatment of nasopharyngeal carcinoma.

【 授权许可】

Unknown   
© Liu 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.