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

Journal of Translational Medicine

Wenlin Huang¹  Jiang-xue Wu²  Liang Kang⁵  Huan-xin Lin²  Hong-yu Han²  Lan-cai Zhu²  Hong-li Li⁴  Peng Zhao³  Ling Zhou²  Ying-hui Zhu²  Ran-yi Liu² 

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

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

Others  :  1205887
DOI  :  10.1186/1479-5876-10-256

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

【 摘 要 】

Background

Interferon-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.

Methods

The 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.

Results

The 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.

Conclusions

These 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】

   
2012 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

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