GROWTH ADVANTAGE OF COX-2 EXPRESSING PANCREATIC CANCER CELLS IN VITRO AND IN VIVO

Abstract

Cyclooxygenase-2 (COX-2) contributes to the phenotype of human malignancies. Targeting the COX-2 pathway is considered an intriguing approach for therapy and prevention of several human tumors, including pancreatic cancers (PaCa). However, the molecular signals underlying the pro-tumorigenic properties of COX-2 are poorly described. The aim of the present study was to characterize the phenotype of COX-2 expressing human PaCa cells. MIA PaCa-2 (MP2) cells, which lack COX-2 expression, were stably transduced with lentiviruses encoding for human COX-2 and FACS-sorted to yield ≥95% pure cell populations (MP2−COX2 and MP2+COX2). Western blot confirmed stable COX-2 expression. Anchorage-dependent (cell count, MTT) and -independent (Matrigel) growth assays demonstrated an increase in cell growth in MP2+COX2 cells. Using a Human Apoptosis PCR Array significant differences were detected between MP2+COX2 and MP2-COX2 cells in several genes, including members of the bcl-2 family. A subcutaneous xenograft model in nude mice demonstrated bigger MP2+COX2 tumors at 2 weeks (294 ± 135 vs. 122 ± 48 mm3; p < 0.05). We have established a model to precisely study the role of COX-2 in human pancreatic cancer cells. Over-expression of COX-2 in pancreatic cancer cells correlated with an enhanced growth in vitro and in vivo. These findings will provide the basis for more mechanistic studies on the role of COX-2 in pancreatic cancer and may help to develop novel therapeutic strategies in pancreatic cancers aiming at the COX-2 pathway.