The relationship between the antitumor effect of the IL-12 gene therapy and the expression of Th1 cytokines in an HPV16-positive murine tumor model

Mediators Inflamm. 2014:2014:510846. doi: 10.1155/2014/510846. Epub 2014 Apr 7.

Abstract

Objective: The goal of the present study was to investigate the effect of IL-12 expressed in plasmid on the Th1 cytokine profile in an experimental HPV16-positive murine tumor model and the association with the IL-12's antitumor effect.

Methods: Mice were injected with BMK-16/myc cells to establish HPV16-positive tumor and then pNGVL3-mIL-12 plasmid; pcDNA3 plasmid or PBS was injected directly into tumor site. The antitumor effect of the treatment was evaluated and the cytokines expression profile in each tumor tissue was analyzed.

Results: Treatment with pNGVL3-mIL-12 plasmid had a significant antitumor effect, and a Th2-Th3-type cytokines prolife was detected in the murine tumor model with expression of the cytokines IL-10, IL-4, and TGF-β1. However, after the tumor was treated with three intratumoral injections of plasmid containing IL-12 cDNA, it showed a cytokine profile associated with Th1 with expression of IL-2, IL-12, and IFN-γ cytokines and reduced expression of IL-10, IL-4, and TGF-β1.

Conclusions: The treatment with the IL-12 gene in the experimental HPV16-positive tumor model promoted the activation of the cellular immune response via expression of a Th1-type cytokine profile and was associated with the inhibition of tumor growth. Thus, IL-12 treatment represents a novel approach for gene therapy against cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Female
  • Genetic Therapy
  • Human papillomavirus 16 / pathogenicity*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism*
  • Interleukin-4 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Plasmids
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th1 Cells / metabolism*

Substances

  • Cytokines
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma