Cyclooxygenase-2 confers growth advantage to syngeneic pancreatic cancer cells

• Published in: Pancreas Vol. 40; no. 3; p. 453
• Main Authors: Takahashi, Hiroki, Li, Aihua, Dawson, David W, Hines, Oscar Joe, Reber, Howard A, Eibl, Guido
• Format: Journal Article
• Language: English
• Published: United States 01.04.2011
• Subjects: Animals; Apoptosis - genetics; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - physiology; Dinoprostone - biosynthesis; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Pancreatic Neoplasms - enzymology; Pancreatic Neoplasms - etiology; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Transduction, Genetic; Transplantation, Heterologous
• ISSN: 1536-4828
• DOI: 10.1097/mpa.0b013e31820b9733

Targeting the cyclooxygenase-2 (COX-2)/prostanoid pathway is considered an intriguing approach for therapy and prevention of several cancers. However, the molecular mechanisms that underlie the protumorigenic properties of COX-2 in pancreatic cancer (PaCa) are still poorly understood. The purpose of the present study was to characterize the phenotype of COX-2 expressing syngeneic PaCa cells. Cyclooxygenase-2-negative MIA PaCa-2 cells were stably transduced with COX-2 or control viruses (MP2 and MP2). Prostaglandin E2 (PGE2) production was measured by liquid chromatography and tandem mass spectrometry. Anchorage-dependent and -independent cell growth was analyzed by cell count and 3-dimensional collagen cell culture system, respectively. Changes in apoptotic gene expression were measured by a polymerase chain reaction array. The growth of tumors in vivo was evaluated in a xenograft animal model. Stable expression of COX-2 increased anchorage-dependent and -independent cell growth, which was accompanied by elevated PGE2 production. Several significant differences in apoptotic gene expression were detected between MP2 and MP2 cells. Furthermore, MP2 cells grew faster than MP2 cells in a xenograft animal model. Our results will provide the basis for more mechanistic studies on the role of COX-2 in PaCa and may help to develop novel therapeutic strategies aiming at the COX-2/prostanoid pathway.