Impacts of Cytosolic Phospholipase A2, 15-Prostaglandin Dehydrogenase, and Cyclooxygenase-2 Expressions on Tumor Progression in Colorectal Cancer

Abstract

PurposeIn addition to cyclooxygenase-2 (COX-2) which is related to prostaglandin E2 synthesis, other enzymes such as cytosolic phospholipase A2 (cPLA2), microsomal prostaglandin E2 synthase-1 (mPGES-1), and 15-prostaglandin dehydrogenase (15-PGDH) have been suggested to be related to carcinogenesis of colorectal cancer (CRC). The aim of this study was to investigate the roles of cPLA2, COX-2, mPGES-1, and 15-PGDH in tumor progression.Materials and MethodscPLA2, COX-2, mPGES-1, 15-PGDH, and vascular endothelial growth factor (VEGF) expressions were immunohistochemically examined in 89 CRC, and their expressions were compared with each other or clinicopathologic parameters as well as VEGF as tumor progression parameters.ResultscPLA2 was expressed in 54.5%, COX-2 in 80.5%, mPGES-1 in 96.4%, 15-PGDH in 46.1%, and VEGF in 65.9%. The expression of cPLA2 correlated with VEGF expression. COX-2 expression was correlated with the depth of invasion, tumor stage, cPLA2, and VEGF expressions. Moreover, VEGF revealed the highest expression in the tissues positive for both cPLA2 and COX-2. Furthermore, 15-PGDH expression was inversely correlated with VEGF expression.ConclusionThe present study demonstrates that cPLA2 and mPGES-1, in addition to COX-2, are constitutively overexpressed, and that 15-PGDH might be attenuated in colorectal cancer. Furthermore, cPLA2 and 15-PGDH as well as COX-2 could have an important role in tumor progression.

Non-Steroidal Anti-Inflammatory Drugs, DNA Repair and Cancer

“…Cytosolic phospholipase A 2 (cPLA2) expression is decreased in NIH 3T3 cells treated with either aspirin or sulindac (Yuan et al, 2000) and in CRC cell lines (SW480, Colo320 and HT-29) when treated with low mM (2.5-10) concentrations of aspirin (Yu et al, 2003). This observation is intriguing given that cPLA 2 expression has been proposed to participate in intestinal tumorigenesis (eg (Lim et al, 2010) and refs therein). Law et al have indicated that (high mM concentrations of) salicylate (in Balb/MK cells) can inhibit the activity and phosphorylation of the mitogen activated protein kinase, p70 s6k independent of p38 MAPK, with a concomitant reduction in DNA synthesis, cell proliferation and in expression of proliferation associated proteins such as c-MYC, cyclin D1, and PCNA and led the authors to conclude that salicylate may act via the mTOR pathway (Law et al, 2000).…”

Recovery of Genes Epigenetically Altered by the Histone Deacetylase Inhibitor Scriptaid and Demethylating Agent 5-Azacytidine in Human Leukemia Cells

“…A recent study reported the association of a risk of lung cancer with an HPGD SNP (Wang et al, 2010). It is inversely correlated with VEGF expression in colorectal cancer (Lim et al, 2010). HPGD is down-regulated in gastric cancer (Thiel et al, 2009).…”

Prognostic Value of Combined; Cox-2, Cyclin D1 and P21 Expression in Colorectal Cancer (CRC) Patients: An Immunohistochemical Study

“…who found higher expression of COX2 in advanced-stage than in early-stage CRC. Also Lim et al [23], proved that increased COX2 expression was related to depth of invasion and advanced stage.…”