Effects of Interferon-γ and Interleukin-4 on Proliferating Cell Nuclear Antigen Expression in Transplanted Bone Tumor Tissue

Abstract

The rabbit VX2 bone tumor model is an ideal animal model for studying malignant bone tumors. Cytokines have been reported to play a role in tumor initiation and promotion, angiogenesis, and metastasis. However, few studies have investigated the relationship between cytokines and VX2 bone tumor development. This study investigated the effect of interferon-γ (IFN-γ) and interleukin-4 (IL-4) on proliferating cell nuclear antigen (PCNA) expression in tumor tissue. Thirty Japanese white rabbits were randomly divided into group A (n = 15) and group B (n = 15). The rabbit VX2 bone tumor model was constructed by implanting VX2 tumors on the medial side of the upper tibia. Group A was sacrificed in the first week of implantation, and group B in the second week of implantation. Peripheral venous blood, tumor tissue from the medullary cavity at the implantation site, and surrounding bone and soft tissue were harvested before implantation and execution in both experimental groups. IFN-γ and IL-4 expression levels in peripheral blood and PCNA levels in tumor tissues were measured by enzyme-linked immunosorbent assay (ELISA). The tumor tissue of the medullary cavity and surrounding bone and soft tissue was harvested for pathological examination. By the end of the experiment, 30 rabbits were included in the study. There was no significant difference in IFN-γ, IL-4 and PCNA expression levels in group A compared to group B before implantation (t = 1.187, p value = 0.255; t = 1.282, p value = 0.221; t = 0.499, p value = 0.626). IFN-γ and IL-4 expression levels before execution in group A were not significantly different from those before implantation (t = -1.280, p value = 0.213; t = 0.952, p value = 0.349), and PCNA expression levels were higher than those before implantation (t = 2.469, p value = 0.020). Group B had significantly lower IFN-γ expression levels before execution than before implantation (t = -3.741, p value = 0.001) and significantly higher IL-4 and PCNA expression levels before execution than before implantation (t = 6.279, p value < 0.01; t = 13.031, p value < 0.001). IFN-γ expression levels before execution in group B was significantly lower than those before execution in group A (t = 17.184, p value < 0.001), and IL-4 and PCNA expression before execution in group B was significantly higher than that before execution in group A (t = -26.235, p value < 0.001; t = -24.619, p value < 0.001). The correlation between IFN-γ and PCNA levels before execution in groups A and B was negative (r = -0.566, p value = 0.028; r = -0.604, p value = 0.017), and the correlation between IL-4 and PCNA levels was positive (r = 0.583, p value = 0.023; r = 0.884, p value < 0.001). In the rabbit VX2 bone tumor model, extending the period of time after tumor implantation resulted in a negative correlation between IFN-γ and PCNA levels and a positive correlation between IL-4 and PCNA levels.