RESUMEN
Neural cell adhesion molecule 1 (NCAM1/CD56) is expressed on immune cells, myoblasts, and malignant cells, and there is a growing demand for the genetic detection of CD56 and CD56-targeted therapy. In the present study, we developed a novel peptide ligand (designated Natein) that binds to human CD56 by using T7 phage display technology. Natein recognized the extracellular region of CD56 and could bind to natural killer (NK) cells and CD56-positive (CD56+) cancer cells. CD56+ cells enriched from human peripheral blood mononuclear cells (PBMCs) using biotinylated Natein-conjugated microbeads, similarly to CD56 antibody-isolated cells, demonstrated functional cytotoxicity against K562 cells. In addition, Natein could be used to stain CD56+ lymphoma cells in nasal-type extranodal NK/T-cell lymphoma tissues similarly to a CD56 antibody. These findings suggest that Natein has the potential to be alternative to CD56 antibody that could be used for peptide-based cell isolation and diagnosis.
Asunto(s)
Antígeno CD56/antagonistas & inhibidores , Descubrimiento de Drogas , Péptidos/farmacología , Técnicas de Visualización de Superficie Celular , Descubrimiento de Drogas/métodos , Humanos , Inmunoconjugados/farmacología , Células K562 , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Biblioteca de Péptidos , Péptidos/química , Unión ProteicaRESUMEN
OBJECTIVE: To explore the molecular mechanisms of celecoxib-induced pancreatic cancer suppression in vivo and in vitro. METHODS: The anti-pancreatic cancer activities of celecoxib (0, 20, 60 and 100⯵mol/L) were investigated by cell viability and migration of Panc-1 and Bxpc-3â¯cells in vitro. The expression of L1CAM in pancreatic cancer and adjacent tissues was compared using immunohistochemistry. The expressions of L1CAM, STAT3, p-STAT3, NF-κB, p-NF-κB were determined by western blotting, and cell invasive ability was determined by wound healing assay in L1CAM-silenced and over-expressed Panc-1and Bxpc-3â¯cells. RESULTS: The expression of L1CAM in pancreatic carcinoma was stronger than that in the adjacent tissues and L1CAM could increase the growth and invasion of pancreatic cancer cells. Over-expression of L1CAM activated the STAT3/NF-κB signaling pathway in Panc-1 and Bxpc-3 pancreatic cancer cells and celecoxib inhibited their viability and the expressions of STAT3, p-STAT3, NF-κB, p-NF-κB as well as full length L1CAM in a concentration dependent manner. CONCLUSIONS: L1CAM was highly expressed in pancreatic cancer tissue and positively correlated with age, TNM staging and tumor differentiation. L1CAM activated the STAT/NF-κB signaling pathway and celecoxib could inhibit the activity of L1CAM, STAT3 and the NF-κB signaling pathway resulting in decreased growth and invasion of pancreatic cancer cells.