Antitumor effects of interferon-alpha on cell growth and metastasis in human nasopharyngeal carcinoma

Curr Cancer Drug Targets. 2012 Jun;12(5):561-70. doi: 10.2174/156800912800673293.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Carcinoma
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 6 / genetics
  • Cyclin-Dependent Kinase 6 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • G1 Phase / drug effects
  • G1 Phase / genetics
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Interferon-alpha / pharmacology*
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Necrosis / drug therapy
  • Necrosis / genetics
  • Necrosis / metabolism
  • Neoplasm Metastasis
  • Recombinant Proteins / pharmacology
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism

Substances

  • Antineoplastic Agents
  • CCND1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Interferon-alpha
  • Recombinant Proteins
  • Retinoblastoma Protein
  • Cyclin D1
  • Interleukin-12
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6