Variation in cyclooxygenase expression levels within the colorectum

Abstract

The positive association of decreased risk of colorectal cancer with nonsteroidal antiinflammatory drug (NSAID) use, combined with the observation that cyclooxygenase(COX)-2 is present in a majority of colorectal tumors, has led to the proposed use of isozyme-specific COX inhibitors as preventive agents in polyp and tumor formation in the colon. However, the exact biochemical mechanisms and disease stage at which reduced risk is mediated remain somewhat controversial, in part because of the complex biochemical changes that occur during the progression from aberrant crypt to polyp to tumor. In this study, COX-1 and COX-2 protein expression levels were determined in sets of tumor and normal colon tissue. Changes were characterized in COX-1 and COX-2 expression within individuals, in relation to such factors as sex, tumor grade, and location in the colorectum. COX-1 expression levels were found to be significantly reduced in tumors compared to matched normal tissues (Dunn's method, P < 0.05). Additionally, COX-1 expression was decreased in stage T3 tumors as compared to stage T2 tumors (Student's t-test, P = 0.009). Similar to previous reports, COX-2 protein expression was present in 73% of the tumors studied and appeared to be independent of tumor grade and sex. Interestingly, decreased COX-2 expression correlated with tumor occurrence in rectal mucosa (Wilcoxon two-sample test, P < 0.05). These results warrant further investigation, especially the identification of determinants that would predict which populations would be most responsive to COX-2 inhibition as a means of colorectal cancer chemoprevention.

In Vitro Effects on Polydextrose by Colonic Bacteria and Caco-2 Cell Cyclooxygenase Gene Expression

“…The role of COX-1, however, has been less studied. It was reported recently that although previously believed to be constitutively expressed, COX-1 expression may be altered during cancer development (48). According to the results we present here and in a previous study, it can be strongly inducible in the Caco-2 cell line (35).…”

Nonsteroidal Anti-inflammatory Drugs and Subsite-Specific Colorectal Cancer Incidence in the Iowa Women's Health Study

“…COX expression has been reported to vary depending on the site of colorectal cancer. One study reported significantly lower COX-2 expression levels in rectal versus colon tumors (60). In contrast, another study reported a significantly higher prevalence of up-regulated COX-2 in cancerous tissue originating from rectum compared with that from colon (61).…”

Selective Cyclooxygenase-2 Inhibitors and Non-small Cell Lung Cancer

“…For example, benzo[a]pyrene, a polycyclic aromatic hydrocarbon in tobacco smoke and chargrilled foods, can stimulate transcription of COX-2 [18]. In turn, COX-2 catalyses the conversion of benzo[a]pyrene-7,8-diol to benzo[a]pyrene-7,8-diol-9,10-epoxide, which binds to DNA [31]. Benzo[a]pyrene mediated induction of COX-2 may facilitate its own conversion to benzo[a]pyrene-7,8-diol-9,10-epoxide, amplifying the effect on tumour initiation of a given dose of benzo[a]pyrene.…”

“…Peroxidase activity of COX catalyses the conversion of procarcinogens such as benzo[a]pyrene to carcinogens [30,31]. Substantial amounts of xenobiotics can be oxidised to mutagens by the peroxidase activity of COX.…”