Published online Aug 21, 2014. doi: 10.3748/wjg.v20.i31.10729
Revised: January 30, 2014
Accepted: April 8, 2014
Published online: August 21, 2014
The interplay between inflammation and cancer progression is a growing area of research. A combination of clinical, epidemiological, and basic science investigations indicate that there is a relationship between inflammatory changes in the pancreas and neoplastic progression. Diets high in ω-6 polyunsaturated fatty acids provide increased substrate for arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) to form eicosanoids. These eicosanoids directly contribute to pancreatic cancer cell proliferation. Both COX-2 and 5-LOX are upregulated in multiple cancer types, including pancreatic cancer. In vitro studies using pancreatic cancer cell lines have demonstrated upregulation of COX-2 and 5-LOX at both the mRNA and protein levels. When COX-2 and 5-LOX are blocked via a variety of mechanisms, cancer cell proliferation is abrogated both in vitro and in vivo. The mechanism of COX-2 has been shown to include effects on apoptosis as well as angiogenesis. 5-LOX has been implicated in apoptosis. The use of COX-2 and 5-LOX inhibitors in clinical studies in patients with pancreatic cancer has been limited. Patient enrollment has been restricted to those with advanced disease which makes evaluation of these drugs as chemopreventive agents difficult. COX-2 and 5-LOX expression have been shown to be present during the early neoplastic changes of pancreatic cancer, well before progression to invasive disease. This indicates that the ideal role for these interventions is early in the disease process as preventive agents, perhaps in patients with chronic pancreatitis or hereditary pancreatitis.
Core tip: This review article highlights the relationship between inflammation and pancreatic cancer, specifically focusing on the enzymes cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). The role of inflammation and tumor progression is a burgeoning area of research. This review delves into the research that has been conducted investigating COX-2 and 5-LOX and their relationship to pancreatic cancer both in vivo and in vitro. We discuss a variety of investigations including basic science, epidemiological, and clinical as they relate to pancreatic inflammation and eicosanoids.