Cellular prion protein (PrP^C), a glycosylphosphatidylinositol-anchored membrane protein, was found in our lab to be widely expressed in gastric cancer cell lines. In order to evaluate its biological significance in human gastric cancer, we investigated its expression in a large series of gastric tissue samples (n = 124) by immuno histochemical staining with the monoclonal antibody 3F4. Compared with normal tissues, gastric adenocarcinoma showed increased PrP^C expression, correlated with the histopathological differentiation (according to the WHO and Lauren classifications) and tumor progression (as documented by pTNM staging). To better understand the underlying mechanism, we introduced the PrP^C and two pairs of RNAi into the poorly differentiated gastric cancer cell line AGS and found that PrP^C suppressed ROS and slowed down apoptosis in transfected cells. Further study proved that the apoptosis-related protein Bcl-2 was upregulated whereas p53 and Bax were downregulated in the PrP^C-transfected cells. A reverse effect was observed in PrP^C siRNA-transfected cells. These results strongly suggested that PrP^C might play a role as an effective antiapoptotic protein through Bcl-2-dependent apoptotic pathways in gastric cancer cells. Further study into the mechanism of these relationships might enrich the knowledge of PrP, better our understanding of the nature of gastric carcinoma, and further develop possible strategies to block or reverse the development of gastric carcinoma.

ABSTRACT. This study aimed to investigate the effect of inhibitors of the NF-kΒ alpha mutant gene (IkBaM) delivery to mensenchymal stem cells (MSCs) on rat chronic pancreatitis (CP). A total of 120 SpragueDawley rats were randomly divided into 6 groups of 20: Group A was injected with sterile saline solution, Group B was injected with allogenic MSCs, Group C1 was injected with allogenic IkBαM-MSCs cultured in vitro 4 h before CP modeling, Group C2 was injected with allogenic IkBαM-MSCs cultured in vitro during CP modeling, Group C3 was cultured with allogenic IkBαM-MSCs cultured in vitro 4 h after CP modeling, and Group D was injected with rAAV2-MSCs. Cytokine levels of ICAM-1, CTGF, IL-1, IL-6, IL-8, TNF-α, TIMP-1, TIMP-2, IL-10, FN, MMP-1, MMP-2, MMP-3, and MMP-9 were examined. The results indicated that allogenic IκBαM-MSCs could reduce pro- inflammatory cytokine levels and increase anti-inflammatory cytokine levels in CP. The allogenic IkBαM-MSCs reduced the activation and promoted the apoptosis of pancreatic stellate cells in the rat model of CP. IkBαM-MSCs influenced the proliferation and apoptosis of pancreatic stellate cells by regulating the activation of the PPAR, MAPK, mTOR, TGF-β, NOD-like receptor, Notch, WNT, TGF-β1-SMAD-2/3, and P53 signal transduction pathways.