Abstract
Nasopharyngeal carcinoma (NPC) is a highly malignant and frequently metastasized tumor, and the prognosis is very poor when distant metastases occur. Recently, immunotherapy is becoming a promising therapeutic approach. Interferon-α (IFN-α) represents the cytokines exhibiting the longest record of use in clinical oncology. In this study, we examined the antitumor effects of IFN-α1b on NPC. The results showed that recombinant human IFN-α1b (hIFN-α1b) suppressed cell growth, induced a G1-phase cell cycle arrest in vitro, increased the expression of p16 and pRb, and decreased the expression of CCND1 and CDK6. In vivo analyses showed that either recombinant adeno-associated virus (rAAV)-IFN-α1b or hIFN-α1b treatment inhibited tumor growth and metastasis, reduced intratumoral microvessel density, increased cell apoptosis and necrosis, and induced prolonged survival. Notably, rAAV-IFN-α1b or hIFN-α1b treatment led to significantly higher serum levels of IL-12 and GM-CSF in mice compared to respective controls. Our findings suggest that IFN-α1b acts as a multifunctional antitumor agent in NPC, which may have important therapeutic implications.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Apoptosis / genetics
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Carcinoma
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Cell Cycle Checkpoints / drug effects
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Cell Cycle Checkpoints / genetics
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cyclin D1 / genetics
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Cyclin D1 / metabolism
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Cyclin-Dependent Kinase 6 / genetics
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Cyclin-Dependent Kinase 6 / metabolism
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Cyclin-Dependent Kinase Inhibitor p16 / genetics
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Cyclin-Dependent Kinase Inhibitor p16 / metabolism
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G1 Phase / drug effects
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G1 Phase / genetics
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Gene Expression / drug effects
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Gene Expression / genetics
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Humans
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Interferon-alpha / pharmacology*
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Interleukin-12 / genetics
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Interleukin-12 / metabolism
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Nasopharyngeal Carcinoma
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Nasopharyngeal Neoplasms / drug therapy*
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Nasopharyngeal Neoplasms / genetics
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Nasopharyngeal Neoplasms / metabolism
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Nasopharyngeal Neoplasms / pathology
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Necrosis / drug therapy
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Necrosis / genetics
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Necrosis / metabolism
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Neoplasm Metastasis
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Recombinant Proteins / pharmacology
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Retinoblastoma Protein / genetics
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Retinoblastoma Protein / metabolism
Substances
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Antineoplastic Agents
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CCND1 protein, human
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Cyclin-Dependent Kinase Inhibitor p16
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Interferon-alpha
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Recombinant Proteins
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Retinoblastoma Protein
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Cyclin D1
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Interleukin-12
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Granulocyte-Macrophage Colony-Stimulating Factor
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CDK6 protein, human
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Cyclin-Dependent Kinase 6