Inhibitory effects of human lactoferrin on U14 cervical carcinoma through upregulation of the immune response

Human lactoferrin (hLF) is a multifunctional glycoprotein that inhibits cancer growth. However, the inhibitory effect of this glycoprotein in cervical cancer remains inconclusive. This study investigated the efficacy of hLF on the inhibition of U14 cervical cancer in vivo. Recombinant adenovirus carrying hLF (Ad-hLF) were constructed. Mice inoculated with U14 cells were randomly allocated to four treatments: i) Phosphate-buffered saline (negative control), ii) Ad-green fluorescent protein (negative control), iii) Ad-hLF (studied) or iv) cyclophosphamide (CTX; positive control). Tumor growth, as well as levels of natural killer (NK) cells, CD4(+) and CD8(+) peripheral blood T lymphocyte subpopulations, serum cytokines and vascular endothelial growth factor (VEGF) in tumor tissues were detected. Compared with the negative controls, tumor growth was inhibited by hLF and mice lifespans in the Ad-hLF-treated group were prolonged to reach the levels of the CTX-treated group. The activity of tumor-killing NK cells was upregulated by hLF. Moreover, the number of CD4(+) and CD8(+) peripheral blood T lymphocyte subpopulations increased following treatment with Ad-hLF. Treatment with Ad-hLF increased the levels of serum interferon-γ, serum interleukin-2 (IL-2) and tumor necrosis factor-α, and decreased the levels of serum IL-4 in tumor-bearing mice. The expression of VEGF in tumor tissues was downregulated by hLF. In conclusion, hLF inhibits the growth of U14 solid tumors by modulating the immune response of tumor-bearing mice.