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

• Published in: Mediators of Inflammation 2014-01, Vol.2014 (5), p.236-244
• Main Authors: García Paz, Flor, Madrid Marina, Vicente, Morales Ortega, Ausencio, Santander González, Abimelec, Peralta Zaragoza, Oscar, Burguete García, Ana, Torres Poveda, Kirvis, Moreno, José, Alcocer González, Juan, Hernandez Marquez, Eva, Bermúdez Morales, Victor
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2014/510846

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.