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

Abstract

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.

• Authors: Ran-yi Liu, Ying-hui Zhu, Ling Zhou, Peng Zhao, Hong-li Li, Lan-cai Zhu, Hong-yu Han, Huan-xin Lin, Liang Kang, Jiang-xue Wu, Wenlin Huang
• Journal: Journal of translational medicine (J Transl Med) Vol. 10 Pg. 256 (Dec 28 2012) ISSN: 1479-5876 [Electronic] England
• PMID: 23272637 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon-gamma

Topics

• Adenoviridae (genetics)
• Animals
• Apoptosis
• Carcinoma
• Cell Proliferation
• Female
• G1 Phase Cell Cycle Checkpoints
• Gene Transfer Techniques
• Genetic Therapy
• Humans
• Interferon-gamma (genetics, therapeutic use)
• Mice
• Mice, Nude
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (pathology, therapy)
• Xenograft Model Antitumor Assays