NS-398 promotes pancreatic cancer cell invasion by CD147 and MMP-2 via the activation of P38

The overexpression or abnormal activation of cyclo-oxygenase-2 (COX-2) has been reported in pancreatic cancer cells. NS-398, a selective inhibitor of COX-2, is unable to inhibit pancreatic cancer cell proliferation, as determined by a Cell Counting Kit 8 assay. However, it does increase cancer cell invasiveness, and therefore the invasiveness of the PANC-1 cells was determined, along with the activation of P38, which was assessed by western blotting. In the present study, to evaluate the mechanisms underlying the action of NS-398 in pancreatic cancer cells, PANC-1 cells were treated with NS-398, and the invasion signaling pathways of cluster of differentiation (CD)147-matrix metalloproteinase (MMP)-2 and mitogen-activated protein kinases were evaluated. The results showed that NS-398-induced the expression of CD147 and MMP-2 via the activation of P38, which was involved in antiproliferative activity and induced pancreatic cancer cell invasiveness. The PANC-1 cells were also co-treated with CD147 small interfering (si)RNA and NS-398, and it was found that the NS-398-induced activation of P38 was not inhibited by CD147 siRNA, however, the expression of MMP-2 was inhibited. CD147 siRNA inhibited the invasiveness of the pancreatic cancer cells induced by NS-398, but also restored NS-398-induced antiproliferative activity. These data indicated that P38 in the pancreatic cancer cells was non-specifically activated by NS-398. This activation induced the expression of CD147-MMP-2, opposed the antiproliferative activity of NS-398 and increased the invasiveness of the PANC-1 cells.