Chemoprevention of Cancers in Gastrointestinal Tract with Cyclooxygenase 2 Inhibitors

Rui      Wang; Linjie      Guo; Pu      Wang; Wenjuan      Yang; Yaoyao      Lu; Zhiyin      Huang; Chengwei      Tang

doi:10.2174/1381612811306010115

Abstract

The finding that cyclooxygenase-2 (COX-2) is over-expressed and plays an important role in carcinogenesis in gastrointestinal (GI) cancers including esophagus, gastric and colorectal cancers has triggered the researches of COX-2 inhibitors as the chemopreventive option for GI cancers. This reviewer updates the current molecular biology on the regulation of COX-2 expression, pharmacological concepts of COX-2 inhibitors in the chemoprevention of GI tract, the clinical efficacies of COX -2 inhibitors in prevention of cancers in GI tract and associated main adverse events. In inflammation, COX-2 expression is regulated both at the transcriptional and posttranscriptional levels. Hypermethylation of the CpG island in the COX-2 gene is the major cause of COX-2 silencing in a subset of GI cancers. However, the tumor-inhibitory efficacy of non-selective non-steroidal antiinflammatory drugs (NSAIDs) or selective COX-2 inhibitors is not necessarily related to their COX-inhibitory potential. These compounds harbor additional pharmacological activities that are entirely independent of its COX-2 inhibitory activity. The clearly identified targets relevant for anticancer therapy, the benefits from clinical chemoprevention of GI tract cancers and the absence of adverse findings of cardiovascular function or histopathology in preclinical toxicology studies indicate the promising results of COX-2 inhibitors. The efficacy and toxicity of NSAIDs are a consequence of the inhibition of the COX enzymes. Therefore, an optimal regime of COX-2 inhibitors in chemoprevention of GI cancers should be further investigated probably by adjustment of dosage, duration, integration of co-therapy and careful selection of candidates.

Keywords: Cyclooxygenase 2, esophagus cancer, gastric cancer, colorectal cancer, Cyclooxygenase 2 inhibitor, aspirin, celecoxib, rofecoxib, carcinogenesis, dosage