Celecoxib suppresses proliferation and metastasis of pancreatic cancer cells by down-regulating STAT3 / NF-kB and L1CAM activities

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 μmol/L) were investigated by cell viability and migration of Panc-1 and Bxpc-3 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-3 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.