Suppression of FAK by nexrutine inhibits gastric cancer progression.

AIM: Nexrutine, an herbal extract of Phellodendron amurense, has been found to play a tumor-suppressive role in many cancers. However, its role in the pathogenesis of gastric cancer remains unclear. MATERIALS AND METHODS: Gastric cancer cells (SGC-7901 and MGC-803) were treated with nexrutine, and cell proliferation, invasion and apoptosis were analyzed. And the MGC-803 cells-derived xenograft mouse models were fed pelleted diet containing 600 mg/kg nexrutine for 21 days after inoculation. Mechanically, we focused on the influences of nexrutine on the levels and activation of STAT3 and NF-κB as well as their upstream regulator FAK. Additionally, we further verified whether nexrutine affected the proliferation, invasion and apoptosis of gastric cancer cells via FAK by upregulating FAK expression before nexrutine treatment. KEY FINDINGS: We found nexrutine inhibited the viability, invasion, and expression levels of PCNA, CyclinD1 and Bcl-2, promoted the apoptosis and Bax expression, decreased levels of STAT3, phospho-STAT3, NF-κB p65, phospho-p65, FAK and phospho-FAK in gastric cancer cells. Overexpression of FAK reversed the impacts of nexrutine on the levels of STAT3, phospho-STAT3, NF-κB p65, phospho-p65, as well as the malignant characteristics of gastric cancer cells. Moreover, nexrutine suppressed tumor volumes and weights, and decreased expression and phosphorylation of FAK, STAT3 and NF-κB p65 in vivo. SIGNIFICANCE: Nexrutine inhibited the malignant progression of gastric cancer via negatively regulating STAT3/NF-κB signaling pathway by suppressing FAK expression and activation.

Effects of dietary yeast nucleotides supplementation on intestinal barrier function, intestinal microbiota, and humoral immunity in specific pathogen-free chickens.

Yeast nucleotides are a fine functional additive in human and animals. The effects of dietary yeast nucleotides supplementation on intestinal development, expression of intestinal barrier-related genes, intestinal microbiota, and infectious bronchitis virus (IBV) antibody titer of specific pathogen-free (SPF) chickens were investigated. A total of 60 1-d-old chickens were divided into 4 groups, each of which included 3 replicates of 5 chickens. Group 1 served as a control that was fed a basal diet. Groups 2 to 4 were fed the basal diet supplemented with 0.1%, 0.3% and 0.5% yeast nucleotides, respectively. All chickens were inoculated intranasally with inactivated IBV vaccine at day 1 and day 10. At day 17, the intestinal development, expression of intestinal barrier-related genes and microbiota were evaluated. There was a significant increased ileal villus height and villus height to crypt depth ratio in group 2 (P < 0.05). Moreover, group 4 exhibited higher expression of zonula occludens-1 (ZO-1) and Occludin gene in ileum (P < 0.05), whereas groups 2 and 3 exhibited higher expression of Mucin 2 (MUC2) and trefoil factor 2 (TFF2) gene (P < 0.05), group 2 showed lower expression of IFN-α gene (P < 0.05). Dietary yeast nucleotides increased intestinal bacterial diversity (P < 0.05), and the abundance of Lactobacillus (P < 0.05). At day 10, 17, 24, 31, 38, and 45, the serum IBV antibody titers were tested. Group 2 exhibited higher IBV antibody titer at day 17 (P < 0.05), furthermore, groups 2 to 4 reached the effective levels 1 wk earlier than control group. In conclusion, dietary yeast nucleotides supplementation can help birds to mount a faster and stronger antibody response to IBV vaccine. In addition, dietary yeast nucleotides supplementation can also promote the intestinal development and barrier-related genes expression, and diversity and richness of intestinal microbiota.