Intra-arterial interleukin-12 gene delivery combined with chemoembolization: anti-tumor effect in a rabbit hepatocellular carcinoma (HCC) model

Abstract

Background: Interleukin-12 (IL-12), a cytokine naturally secreted by activated dendritic cells and monocytes/macrophages, is known as a key anti-tumor agent in many tumor models, including hepatocellular carcinoma (HCC) models.

Purpose: To evaluate the anti-tumor effect of intra-arterial IL-12 gene delivery alone and in combination with transcatheter arterial chemoembolization (TACE) in rabbit VX2 liver cancer model.

Material and methods: Rabbits with VX2 liver tumors were randomized into four groups, eight in each group. After laparotomy and insertion of a 30-gauge needle into the proper hepatic artery, the following interventional procedure protocols were applied: 0.9% saline solution (group A, control), TACE (group B, TACE alone, lipiodol + mitomycin), intra-arterial interleukin-12 gene infusion (group C, IL-12 alone), and intra-arterial interleukin-12 gene infusion in combination with TACE (group D, IL-12 plus TACE). Growth ratio was estimated by computed tomography. To analyze apoptotic index, tumor tissues were explanted for terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining, 14 days after therapy.

Results: Significant differences of the relative tumor growth ratio were observed in TACE alone group and IL-12 plus TACE group in comparison with control (P < 0.05, ANOVA, Tukey's HSD correction) but not between IL-12 alone and control, or IL-12 plus TACE group and TACE alone group (P > 0.05). Significant changes of the apoptotic index were observed in group D in comparison with remaining three groups (P < 0.05). The difference between group C and group A was not significant statistically (P > 0.05).

Conclusion: Intra-arterial interleukin-12 gene therapy combined with TACE has a potent anti-tumor effect in rabbit VX2 liver cancer in comparison with TACE alone.

Keywords: Chemoembolization; anti-tumor; apoptotic index; gene therapy; interleukin-12; liver cancer.