Adenovirus-mediated delivery of interferon-γ gene inhibits the growth of nasopharyngeal carcinoma
- Equal contributors
1 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dong-feng Road East, Guangzhou, 510060, China
2 Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
3 Department of Gastrointestinal Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
4 Department of Colorectal Surgery, the Sixth Affliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
5 Institute of Microbiology, Chinese Academy of Science, Beijing, 100101, China
6 Guangdong Provincial Key Laboratory of Tumor-targeted Drug, Guangzhou Doublle Bioproducts Co., Ltd., Guangzhou, 510663, China
Journal of Translational Medicine 2012, 10:256 doi:10.1186/1479-5876-10-256Published: 28 December 2012
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.
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.
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.
These findings indicate IFN-γ gene therapy mediated by replication defective adenoviral vector is likely a promising approach in the treatment of nasopharyngeal carcinoma.