ABSTRACT
Recombinant human peroxiredoxin-5 (hPRDX5), isolated from anti-cancer bioactive peptide (ACBPs), shows a homology of 89% with goat peroxiredoxin-5 (gPRDX5) and is reported to display anti-tumor activity in vivo. Herein, we explored the effect of hPRDX5 and the responsible mechanism in treating pancreatic cancer. Tumor-bearing mice were randomly divided into normal PBS group and treatment group (n=5; 10 mg/kg hPRDX5). Flow cytometry was employed to examine lymphocytes, myeloid-derived suppressor cell subsets, and the function proteins of natural killer (NK) cells in peripheral blood, spleen, and tumor tissues of mice. Western blot was used to measure the protein expressions of the key nodes in TLR4-MAPK-NF-κB signaling pathway. The rate of tumor suppression was 57.6% at a 10 mg/kg dose in orthotopic transplanted tumor mice. Moreover, the population of CD3+CD4+T cells, NK cells, and CD3+CD8+T cells was significantly increased in the tumor tissue of the hPRDX5 group, while the proportion of granulocytic-myeloid-derived suppressor cells decreased slightly. In addition, after treatment with hPRDX5, the percentage of NK cells in blood increased more than 4-fold. Our findings indicated that hPRDX5 effectively suppressed pancreatic cancer possibly via the TLR4-MAPK-NF-κB signaling cascade; hence hPRDX5 could be a prospective immunotherapy candidate for treating pancreatic cancer.
ABSTRACT
The objective was to study the effect of mechanical intestinal obstruction in rats on the phenotype of interstitial cells of Cajal (ICC). Healthy Wistar rats were randomly divided into sham-operation group (C), one day obstruction group (M1), two days obstruction group (M2), and three days obstruction group (M3), with 10 rats in each group. The expression of SCF mRNA and c-Kit protein in intestinal tissue was investigated by RT-PCR and immunohistochemistry. Compared with the sham-operation group, the relative expression of SCF mRNA and the expression of c-Kit protein in intestinal tissue were significantly decreased in both obstruction groups. Levels decreased gradually with the prolongation of obstruction time, and significantly decreased on the 3rd day after obstruction (P<0.05). Immunohistochemical staining of the small intestine showed that the number of ICC in the sham-operation group was the highest, and they were gradually decreased with the extension of obstruction time in the M1 to M3 groups. There was a significant difference between groups (P<0.05). Intestinal obstruction caused a decrease in the concentrations of SCF mRNA and c-Kit protein in ICC. With the prolongation of intestinal obstruction, the number of ICCs gradually decreased.